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Maternal blood lead concentration, diet during pregnancy, and anthropometry predict neonatal blood lead in a socioeconomically disadvantaged population. (Children's Health).


To determine the influences of maternal diet and nutrition during pregnancy on the blood lead level of neonates, we conducted a study of mother-infant pairs from lower socioeconomic circumstances living in Albany County, New York For the county in Wyoming, see Albany County, Wyoming
Albany County is a county located in the U.S. state of New York, generally located in the vicinity of Albany, New York, the capital of New York State. Albany is also the county seat of Albany County.
. Maternal blood lead (MBPb), anthropometry anthropometry (ănthrəpŏm`ətrē), technique of measuring the human body in terms of dimensions, proportions, and ratios such as those provided by the cephalic index. , and diet were assessed in each trimester trimester /tri·mes·ter/ (-mes´ter) a period of three months.

tri·mes·ter
n.
A period of three months.


Trimester
The first third or 13 weeks of pregnancy.
. Neonates' blood lead (NBPb) levels were low (geometric mean (mathematics) geometric mean - The Nth root of the product of N numbers.

If each number in a list of numbers was replaced with their geometric mean, then multiplying them all together would still give the same result.
 = 1.58 [micro]g/dL), and none had elevated blood lead. More than 50% of the mothers had intakes below the recommended dietary allowances Recommended Dietary Allowance (RDA)
The Recommended Dietary Allowances (RDAs) are quantities of nutrients in the diet that are required to maintain good health in people.
 for zinc, calcium, iron, vitamin D vitamin D

Any of a group of fat-soluble alcohols important in calcium metabolism in animals to form strong bones and teeth and prevent rickets and osteoporosis. It is formed by ultraviolet radiation (sunlight) of sterols (see steroid) present in the skin.
, and kilocalories. As expected, MBPb was strongly and positively related to NBPb. Among the anthropometric an·thro·pom·e·try  
n.
The study of human body measurement for use in anthropological classification and comparison.



an
 measures of maternal nutritional status nutritional status,
n the assessment of the state of nourishment of a patient or subject.
, variables measuring gain in weight and arm circumference were negatively related to NBPb. In multivariable models reflecting different analytic strageties and including MBPb, anthropometry, and sociodemographic characteristics, dietary intakes of iron and vitamin D were negatively related to NBPb. The effect of zinc varied substantially depending on model covariates. Effects of dietary constituents are difficult to distinguish, given the intercorrelated nature of nutrients in the diet. Nevertheless, the influences of maternal anthropometric variables, iron, and vitamin D on neonatal lead levels are clear in our analyses. Key words: anthropometry, calcium, children, diet, iron, lead, neonates, nutrition, zinc. Environ Health Perspect 111:195-200 (2003). [Online 28 October 2002]

doi: 10.1289/ehp.5592 available via http://dx.doi.org/

***********

The average blood lead concentration among young children in the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area.  has decreased markedly since 1980 (Brody et al. 1994; Pirkle et al. 1994); but in many inner-city, socioeconomically disadvantaged communities, worrisome numbers of children continue to be diagnosed with elevated lead levels (Brown et al. 2000; Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center.  2001; LaFlash et al. 2000; Litaker et al. 2000). Lead is related to adverse health effects in children including interference with neurobehavioral development, reduced physical growth, impaired heme synthesis, kidney and liver failure liver failure Clinical medicine Liver insufficiency that results in death, requires a liver transplant, or is characterized by recovery after encephalopathy, or while awaiting a transplant; also defined as a condition with ≥ 3 of following: albumin < 3. , seizures, and even death (ATSDR ATSDR Agency for Toxic Substances & Disease Registry  1988).

A child's lead burden begins before birth with lead transferred from maternal circulation and increases rapidly in the first few years of life, as exposure to environmental lead increases (ATSDR 1988; Brody et al. 1994; Pirkle et al. 1994). During pregnancy, lead is liberated from the maternal skeleton (Gulson et al. 1997) and transferred from mother to child in utero in utero (in u´ter-o) [L.] within the uterus.

in u·ter·o
adj.
In the uterus.



in utero adv.
. It is useful to know the factors that may influence this transfer in order to manipulate them and reduce fetal exposure and its effects. Although many risk factors for lead exposure such as past maternal education or race/ethnicity cannot be altered, maternal diet during pregnancy and nutritional status can be. The goal of this investigation is to determine the influence of these two factors on the concentration of blood lead in the newborn in a socioeconomically disadvantaged population at risk for lead exposure.

Materials and Methods

The Albany Pregnancy Infancy Lead Study (APILS APILS Aim Point Identification Light System ), a prospective, longitudinal study longitudinal study

a chronological study in epidemiology which attempts to establish a relationship between an antecedent cause and a subsequent effect. See also cohort study.
, was initiated to address the question of nutrient-lead interaction and to explore the impact of early lead concentration on infant growth and development (the subject of other reports). The study was conducted in two phases that differed in follow-up protocol and lead concentration measurement methods: phase one from 1986 to 1992 and phase two from 1992 to 1998; both phases have been described elsewhere (Schell et al. 1997, 2000). This report is based on data from the second phase. All procedures for both studies were reviewed and approved by the Institutional Review Boards of the New York New York, state, United States
New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of
 State Department of Health, Albany Medical Center and the State University of New York (body) State University of New York - (SUNY) The public university system of New York State, USA, with campuses throughout the state.  at Albany. Informed consent was obtained before data collection.

Data collection and sample recruitment. The APILS sample was drawn from a socioeconomically disadvantaged population of pregnant women at risk for lead exposure due to poverty, urban residence in old, dilapidated housing, and close proximity to industrial and vehicular emissions. Pregnant women were recruited into the study if they sought prenatal care prenatal care,
n the health care provided the mother and fetus before childbirth.
 at either the Albany County Albany County is the name of two jurisdictions in the United States in different states:
  • Albany County in New York
  • Albany County in Wyoming
 Department of Health (ACDH) Clinic or the Albany Medical Center (AMC (Advanced Mezzanine Card) See AdvancedTCA. ) Obstetrics obstetrics (ŏbstĕ`trĭks), branch of medicine concerned with the treatment of women during pregnancy, labor, childbirth (see birth), and the time after childbirth.  Clinic. Once enrolled, a woman was seen for a study visit once during each trimester of her pregnancy. To be eligible for the study, a participant must a) have been a resident of Albany county; b) have been eligible for the Women, Infants and Children program (WIC WIC - WAN Interface Card ; < 185% of poverty level); c) have been pregnant < 24 weeks; d) have planned to use either the ACDH or AMC clinics for prenatal care for at least two of the three trimesters of pregnancy (depending upon the timing of entry into the study); e) have permitted a cord blood cord blood
n.
Blood present in the umbilical vessels at the time of delivery.
 sample to be taken; and, f) have planned to deliver at AMC and have the child followed at the ACDH or AMC pediatric pediatric /pe·di·at·ric/ (pe?de-at´rik) pertaining to the health of children.

pe·di·at·ric
adj.
Of or relating to pediatrics.
 clinic. Potential participants were excluded if they a) already had a child in the study; b) were unable to complete interviews in English (indicating insufficient linguistic ability to complete the cognitive performance assessment on maternal IQ tests needed to interpret infant development measures); c) were high-risk pregnancies High-Risk Pregnancy Definition

A high risk pregnancy is one in which some condition puts the mother, the developing fetus, or both at higher-than-normal risk for complications during or after the pregnancy and birth.
 (these were referred by clinic staff to a specialized clinic); or d) were pregnancies involving multiple fetuses. Newborns were not excluded on the basis of APGAR score Ap·gar score
n.
A system of evaluating a newborn's physical condition by assigning a value (0, 1, or 2) to each of five criteria: heart rate, respiratory effort, muscle tone, response to stimuli, and skin color.
 or infant size. The sample used in this study represents all the participants recruited into the study between September 1992 and October 1998, when recruitment was completed.

Measurement of blood lead. Maternal blood was drawn in each trimester during a regularly scheduled visit to the prenatal prenatal /pre·na·tal/ (-na´tal) preceding birth.

pre·na·tal
adj.
Preceding birth. Also called antenatal.



prenatal

preceding birth.
 clinic and at delivery by a trained phlebotomist phle·bot·o·mist
n.
1. One who practices phlebotomy.

2. One who draws blood for analysis or transfusion.
 using a lead-free venous blood venous blood
n. Abbr. v
Blood that has passed through the capillaries of various tissues other than the lungs, is found in the veins, in the right chambers of the heart, and in pulmonary arteries, and is usually dark red as a result of a
 collection kit. The infant's cord blood (3 cc) was collected in the delivery room in most cases (90%). When cord blood could not be collected, venous blood (3 cc) was drawn in the neonatal nursery within the first 3 days (except in one case, drawn on day 8). All blood lead measurements were performed by the Wadsworth Center's Lead Poisoning/Trace Elements Laboratory, the New York State Department of Health's reference laboratory for the test. The analytic method for blood lead determination was electrothermal e·lec·tro·ther·mal  
adj.
1. Of, relating to, or involving both electricity and heat.

2. Of or relating to the production of heat by electricity.
 atomization Atomization

The process whereby a bulk liquid is transformed into a multiplicity of small drops. This transformation, often called primary atomization, proceeds through the formation of disturbances on the surface of the bulk liquid, followed by their
 atomic absorption spectrometry Absorption spectrometry
A scientific procedure to determine chemical makeup of samples.

Mentioned in: Herbalism, Traditional Chinese
 with Zeeman background correction; it has been fully validated and described in the literature (Parsons Parsons, city (1990 pop. 11,924), Labette co., SE Kans.; inc. 1871. It is a shipping point for dairy products, grain, and livestock. Manufactures include ammunition, wire and paper products, plastics, and appliances.  and Slavin 1993).

Measurement of maternal diet and nutrition. During each prenatal interview, maternal diet for the month leading up to the interview was assessed using a modified version of the National Cancer Institute Food Questionnaire. The modifications allowed for reporting actual amounts consumed rather than small, medium, or large portions, and for specifying ethnic or foreign foods not included in the food list. A program was written to compute the 30-day intake of 37 macronutrients This is a list of macronutrients. Minerals
  • Calcium
  • Phosphorus
  • Sodium
  • Potassium
  • Chlorine
  • Magnesium
  • Sulfur
Protein
Amino Acids
  • Standard amino acids
, vitamins, and minerals.

Maternal nutritional status with regard to serum Vitamin D (1,25-OH Vitamin D) was assessed in the second and third trimesters Noun 1. third trimester - time period extending from the 28th week of gestation until delivery
trimester - a period of three months; especially one of the three three-month periods into which human pregnancy is divided
 and was analyzed by Metpath Labs, Inc. (Teterboro, NJ). Maternal nutritional status also was assessed at each interview by anthropometric measures including weight, mid-upper arm circumference, and triceps triceps, any muscle having three heads, or points of attachment, but especially the triceps brachii at the back of the upper arm. One head originates on the shoulder blade and two on the upper-arm bone, or humerus.  skinfold skinfold /skin·fold/ (skin´fold) the layer of skin and subcutaneous fat raised by pinching the skin and letting the underlying muscle fall back to the bone; used to estimate the percentage of body fat.  thickness. Height and biepicondylar breadth of the humerus humerus: see arm.  were measured once at the first prenatal visit. The latter measurement is an index of skeletal frame size (Frisancho and Flegel 1983). All measurements were made by one of the authors (L.M.S.) and nurses or graduate research assistants trained by that author using standard, published protocols (Cameron 1986; Lohman et al. 1988). Retraining re·train  
tr. & intr.v. re·trained, re·train·ing, re·trains
To train or undergo training again.



re·train
 sessions were performed at approximately 6-month intervals. Prepregnancy weight was obtained from the medical chart based on subject recall.

The sample. Of the 317 eligible women, 71 terminated their pregnancies, discontinued participation, moved, or transferred care to another facility. In addition, blood from 26 newborns was not drawn at delivery for no medical reason, or was clotted clot  
n.
1. A thick, viscous, or coagulated mass or lump, as of blood.

2. A clump, mass, or lump, as of clay.

3. A compact group: a clot of automobiles blocking the tunnel's entrance.
 and unanalyzable. These losses to the study left 220 newborns with a measured blood lead level at the time of delivery; thus, 220 is the maximum number used for analyses of relationships among mothers' and newborns' lead levels. This sample differs slightly from that used in a previous analysis of APILS data (Schell et al. 2000) because the previous analysis required two consecutive maternal blood lead levels during pregnancy. The blood lead levels of the sample mothers do not differ significantly from those excluded (n = 97) during pregnancy or at delivery; excluded mothers had marginally higher second-trimester blood lead levels than included mothers (2.2 [micro]g/dL and 2.0 [micro]g/dL respectively), though this difference was not statistically significant.

The sample (n = 220) is described in Table 1. Of the 220 mothers, nearly half identified their ethnicity/race as African-American. The median age of the women at time of enrollment was 22.6 years, and 31% of the women were 19 years of age or younger. Mean ages of women did not differ by ethnicity/race. Of the 220 mothers, 59% had completed high school, but 5% had not begun high school; 18% had one or more years of college. Most women (81%) had never been married or were separated or divorced. Median gravidity gravidity Obstetrics The state of being, or having been, pregnant. Cf Gravity.  was three pregnancies, and median parity was one live birth. Sixty percent of the women reported that they were unemployed at the time of their first study visit. Forty-one percent reported that they had been unemployed during the 6 months preceding their first study visit (i.e., 1-5 months before they became pregnant, depending on when in the pregnancy they entered the study). Of the women who worked, most found employment in service occupations in which the hourly pay scale was near minimum wage.

For the analyses of relationships between maternal lead level during pregnancy and the blood lead level of the neonate neonate /neo·nate/ (ne´o-nat) newborn infant.

ne·o·nate
n.
A neonatal infant.



neonate

a newborn animal.
, the sample sizes are reduced because of missing maternal blood lead observations. For further analysis of the relationship between dietary items and neonatal lead levels, the sample was restricted to those mother-neonate pairs with neonatal blood lead and dietary data available from interviews in all trimesters (n = 89). In two cases missing prepregnancy body mass index (BMI BMI body mass index.

BMI
abbr.
body mass index


Body mass index (BMI)
A measurement that has replaced weight as the preferred determinant of obesity.
; weight in kilograms/height in square centimeters) was predicted by regressing other maternal anthropometric measurements anthropometric measurements (anˈ·thrō·p  on prepregnancy BMI for the sample of 220 ([r.sup.2] = 0.96). Six additional cases were missing maternal lead levels and these could not be predicted well by multivariate The use of multiple variables in a forecasting model.  regression, leaving a sample size of 83. These 83 subjects did not differ from excluded subjects (n = 137) in second or third trimester weight; first-, second-, or third-trimester arm circumference or triceps skinfold thickness; maternal age maternal age,
n the age of the mother at the period of conception.
; height; biepicondylar breadth of the humerus; prepregnancy weight or BMI; rate of arm circumference change from the first to second, first to third, or second to the third trimesters; ethnicity/race; education; marital status marital status,
n the legal standing of a person in regard to his or her marriage state.
; first-, second-, and third-trimester intakes of fat, iron, and kilocalories; first-and second-trimester intakes of zinc, protein, vitamin D, and calcium; maternal lead level at birth; or newborn blood lead concentration. Excluded subjects had a lower first-trimester weight than did the 83 included subjects. Maternal intakes of zinc, protein, vitamin D, and calcium in the third trimester were significantly higher among excluded mother-infant pairs.

Data analysis methods. Blood lead concentrations were log transformed due to non-normal distributions. We first determined the relationships between newborn lead level and maternal factors (sociodemographic variables, biochemical measures of nutritional status, and maternal anthropometry) through bivariate bi·var·i·ate  
adj.
Mathematics Having two variables: bivariate binomial distribution.

Adj. 1.
 analysis. Before testing, we noted that years of education are closely related to age in the subsample sub·sam·ple  
n.
A sample drawn from a larger sample.

tr.v. sub·sam·pled, sub·sam·pling, sub·sam·ples
To take a subsample from (a larger sample).
 of women < 19 years of age (r = 0.67, p < 0.001, n = 46). We constructed an education index (EI) of age-appropriate education that is independent of age (r = 0.06, p = 0.397, n = 220) but closely related to maternal education (r = 0.96, p < 0.001, n = 220). For persons < 19, EI = (years of education + 6)/age, and expresses the degree to which they are below or ahead of the age-appropriate year of schooling up to the completion of high school. For persons [greater than or equal to] 19 years of age, presumably pre·sum·a·ble  
adj.
That can be presumed or taken for granted; reasonable as a supposition: presumable causes of the disaster.
 old enough to have completed high school, EI = (years of education + 6)/18 (18 is the age by which a person should have completed high school, allowing for one extra year). Two persons who have completed two years of college, one 40 years old and one 25 years old, have the same El value.

For analysis of maternal dietary effects we created two multivariable models (using the subsample of 83 mother-newborn pairs with complete dietary information) each containing a set of core control variables: prepregnancy BMI, ethnicity, age, education, anthropometry, second-trimester lead, delivery lead, and kilocalories. The latter was included to control for nutrient density The term "nutrient density" has several meanings.

Firstly, nutrient density is defined as a ratio of nutrient content (in grams) to the total energy content (in kilocalories or joules). Nutrient-dense food is opposite to energy-dense food (also called "empty calorie" food).
. We did not include the following variables that were not related to neonatal blood lead in bivariate analysis: maternal arm circumference and triceps skinfold in first and third trimesters; weight in first, second, or third trimesters; maternal height; biepicondylar breadth of humerus; rate of change in maternal triceps skinfold (all trimesters); rate of change in maternal weight and arm circumference from first to second trimester Noun 1. second trimester - time period extending from the 13th to the 27th week of gestation
trimester - a period of three months; especially one of the three three-month periods into which human pregnancy is divided
; second- and third-trimester and delivery serum ferritin ferritin /fer·ri·tin/ (-i-tin) the iron-apoferritin complex, one of the chief forms in which iron is stored in the body.

fer·ri·tin
n.
 and vitamin D; use of dietary supplements during pregnancy; marital status; and employment status. High intercorrelation prevented including all significant anthropometric predictors of newborn lead in the models. Variables were chosen to minimize redundancy among anthropometrics while retaining full explanatory power. The first multivariate model also controlled for calcium (or vitamin D), iron, zinc, protein, and fat. To allow for the impact of intercorrelation among dietary variables in the multivariate model, we constructed a second model with the same core control variables, to which we added one dietary variable at a time, repeating the analysis with a different dietary variable each time. All calculations were performed using SPSS A statistical package from SPSS, Inc., Chicago (www.spss.com) that runs on PCs, most mainframes and minis and is used extensively in marketing research. It provides over 50 statistical processes, including regression analysis, correlation and analysis of variance. , Version 10.1 (SPSS, Chicago, IL). All p-values reported here are from two-tailed (nondirectional) tests.

Dietary intake of calcium, vitamin D, iron, zinc, protein, kilocalories, and fat were compared across trimesters and found not to differ significantly. Because multiple assessments of dietary intake provide a better estimate of true intake (Todd et al. 1983) and the intakes did not differ by trimester, we averaged each nutrient intake across all three trimesters to reduce intrasubject variation and random measurement error (Gibson 1990). In this sample, averaging intakes considerably reduced the variance of dietary intake measures. The variance of the averaged intakes of calcium, iron, fat, kilocalories, vitamin D, and zinc was, on average, only 58% of the individual trimester values.

Results

Blood lead concentrations in this sample are low (Table 2). None of the newborns and only one mother had a blood lead concentration > 10 [micro]g/dL in any single test. The effect of ethnicity/race is evident: African-American mothers and newborns have significantly higher blood lead concentrations than white mothers and newborns, except in the second trimester.

The strongest predictors of newborn blood lead concentration are maternal blood lead concentration in the first, second, and third trimesters and at delivery, as well as the change in maternal blood lead levels from the second trimester to delivery (Table 3). When the sample is restricted to mother-infant pairs with data on blood lead levels in every trimester and at delivery (n = 79), the correlation coefficients Correlation Coefficient

A measure that determines the degree to which two variable's movements are associated.

The correlation coefficient is calculated as:
 are similar to or greater than those presented in Table 3 (data not shown). The correlation between mother's blood lead concentrations and the newborn's is similar in the African-American and white subsamples in every trimester but the first, where sample sizes also are the smallest. Infant blood lead levels are slightly, though significantly, lower than their mother's among both African-American and white subsamples. The transfer of blood lead is similar between the two subsamples when the higher level of blood lead in African-American mothers is taken into account. The difference between mother's and child's blood lead level expressed as percent of the mother's is 19% for whites and 25% for African Americans African American Multiculture A person having origins in any of the black racial groups of Africa. See Race.  (a nonsignificant non·sig·nif·i·cant  
adj.
1. Not significant.

2. Having, producing, or being a value obtained from a statistical test that lies within the limits for being of random occurrence.
 difference).

Effects of maternal nutrition/anthropometric characteristics on newborn blood lead concentration. Several anthropometric measures of maternal nutritional status are related to newborn lead level. Greater rates of gain in maternal weight and arm circumference during the pregnancy are associated with lower blood lead concentration in the newborn (Table 4). Weaker, positive associations exist between blood lead concentrations in the newborn and several other measures of maternal size: prepregnancy BMI, prepregnancy weight, second-trimester arm circumference, and triceps skinfold thickness (Table 4). The correlations among these variables for the white and African-American subsamples are similar in direction and most are similar in magnitude to the correlations for the sample as a whole, except for the effect of second-trimester triceps skinfold and the EI in the white subsample. The two anthropometric measures of skeletal size, maternal height, and biepicondylar breadth of the humerus are unrelated to newborn blood lead level. Other maternal anthropometric measures are unrelated to newborn lead level (data not shown): arm circumferences and triceps skinfolds in the first and third trimesters; maternal weight in the first, second, and third trimesters; rate of change in maternal triceps skinfold across all trimesters; rate of change in maternal weight and arm circumference from the first to second trimester.

Effects of maternal dietary intakes on newborn blood lead concentration. Among women with nutrient intake data for each trimester (n = 83), mean dietary intakes were significantly lower than the recommended dietary allowances (RDAs) for iron and vitamin D, significantly higher than the RDA RDA
abbr.
recommended daily allowance


Recommended Dietary Allowance (RDA)
The Recommended Dietary Allowances (RDAs) are quantities of nutrients in the diet that are required to maintain good health in people.
 for protein, and not significantly different from the RDAs for total caloric caloric /ca·lo·ric/ (kah-lor´ik) pertaining to heat or to calories.

ca·lor·ic
adj.
1. Of or relating to calories.

2. Of or relating to heat.
 intake, calcium, and zinc (Table 5). More than 50% of women were below the RDA for zinc, calcium, iron, vitamin D, and kilocalories.

The first multivariable model, controlling for all other nutrients, shows significant negative relationships between neonatal blood lead and maternal intakes of iron and calcium, but not zinc, protein, or fat (Table 6). When vitamin D is substituted for calcium in the model, the results are similar [vitamin D: [beta] coefficient = -0.013 (SE = 0.007), t = -1.98, p = 0.051]. The second multivariable model in which kilocalories are controlled and one other nutrient is entered into the model produces very similar results (Table 7) in terms of direction of effect and magnitude ([beta] coefficients) for the effects of iron, vitamin D, and calcium except that zinc is a predictor of neonatal lead level in this analysis.

Serum ferritin, serum vitamin D, and the use of supplements were not significant covariates in either multivariable model (data not shown), nor were they significant in bivariate analyses used for model construction.

To estimate the impact of changes in maternal intake of significant micronutrients This is a list of micronutrients.

Vitamins
  • Vitamin A (retinol)
  • Vitamin B complex
  • Vitamin B1 (thiamin)
  • Vitamin B2 (riboflavin)
, we calculated change in newborn lead with changes in maternal intake of iron, calcium, and vitamin D, from one standard deviation In statistics, the average amount a number varies from the average number in a series of numbers.

(statistics) standard deviation - (SD) A measure of the range of values in a set of numbers.
 below the mean intake to one standard deviation above it, using the model and sample described in Table 6. Among these nutrients, maternal iron intake has the largest impact on newborn lead. A two-standard-deviation decrease in iron (from 30.2 to 11.8 mg) is associated with a 0.51 [micro]g/dL increase in newborn lead (29% of the mean of newborn lead, 1.72 [micro]g/dL, n = 83). A two-standard-deviation reduction in calcium (from 1,778 to 583 mg) is associated with an increase of 0.26 [micro]g/dL in newborn lead (15% of the mean of newborn lead), whereas a two-standard-deviation reduction in maternal vitamin D intake, from 10.5 to 2.4 mg, is associated with a 0.18 [micro]g/dL increase in newborn lead, 10% of the mean of newborn lead.

Discussion

Although many of the variables that affect lead levels are difficult to change, maternal diet is potentially modifiable, especially during pregnancy when there may be a supportive environment for maternal and fetal health. However, determining dietary effects of specific nutrients is complicated by covariance Covariance

A measure of the degree to which returns on two risky assets move in tandem. A positive covariance means that asset returns move together. A negative covariance means returns vary inversely.
 among nutrients and wide variation in dietary intake due to intraindividual fluctuation and measurement error. The effect of the latter is apparent in our sample. For any nutrient, the variance of individual trimester intakes is close to twice the variance of the average of the three trimester intakes. The effect of averaging intakes is clear in the APILS sample: Individual nutrient intakes in any trimester are unrelated to newborn lead level in the sample with incomplete dietary data but also in the subsample of 83 mothers with complete dietary data used in our analysis. However, when the intakes across all trimesters are averaged and variances reduced, we observe the relationships reported here.

We employed two analytic approaches to deal with covariance among nutrients, and the results are consistent in both direction and magnitude. After adjustment for control variables (including maternal lead levels), higher maternal iron, calcium, and vitamin D intakes are related to lower newborn lead levels. Evidence for an impact of maternal zinc intake is equivocal EQUIVOCAL. What has a double sense.
     2. In the construction of contracts, it is a general rule that when an expression may be taken in two senses, that shall be preferred which gives it effect. Vide Ambiguity; Construction; Interpretation; and Dig.
. The effect of zinc intake may be absent in the analysis that includes other nutrients as covariates because of its high correlation with protein intake (r = 0.89, p < 0.001). The near universal use of dietary supplements in the sample used for the analysis of diet (78 of 83 mothers) suggests that the effects of dietary iron, calcium, and vitamin D seen here were not biased by differential supplement use. The lack of variability in supplement use also indicates that the absence of its statistical significance in either multivariable model is not a true test of its biologic effect.

Anthropometric measures of maternal nutritional status have a very strong and consistent effect on neonatal lead level: Measures of soft tissue size are positively related to higher newborn lead, whereas measures of gain (e.g., arm circumference during the later half of pregnancy) are related to lower newborn lead concentration. Because heavier women are unlikely to gain as much weight and arm circumference as smaller ones, gain becomes an especially important and modifiable characteristic among smaller women. The relationship of maternal size to neonatal lead level mirrors the positive relationship of maternal caloric intake to neonatal lead level seen in our dietary analysis. The anthropometric measures of skeletal frame size (height and biepicondylar breadth) are not related to neonatal lead levels, suggesting that the size of the skeletal mass as a compartment for lead storage does not affect the transmission of lead from mother to fetus.

Our analysis of maternal diet provides new information on nutrient-lead interactions because it pertains to the transfer of lead from mother to fetus whereas most published research examines relationships of dietary intake and lead levels in either adults or children. In the APILS sample, higher maternal intakes of iron are associated with lower neonatal lead levels, a finding consistent with results from both experimental animal studies (Barton et al. 1978; Crowe and Morgan 1996; Hamilton 1978; Hashmi et al. 1989a, 1989b; Klauder and Petering 1975; Mahaffey-Six and Goyer 1972; Ragan 1977; Shukla et al. 1990; Singh et al. 1991; Suzuki and Yoshida 1979) and human studies (Cheng et al. 1998; Hammad et al. 1996; Mahaffey and Annest 1986; Markowitz et al. 1990; Szold 1974; Watson et al. 1980, 1986; Wright et al. 1999; Yip et al. 1981; Yip and Dallman 1984) that have shown negative associations between iron intake or iron status and blood lead levels. Despite this negative relationship between maternal dietary iron and infant lead levels, we found no significant association between mother's iron stores (serum ferritin) and newborn's blood lead levels in bivariate or multivariate analysis multivariate analysis,
n a statistical approach used to evaluate multiple variables.

multivariate analysis,
n a set of techniques used when variation in several variables has to be studied simultaneously.
 (data not shown), mirroring the results of Milman and colleagues (1988). Because 83% of dietary iron intakes in our sample were less than the RDA for pregnant women, our findings refer most closely to gravidae with suboptimal Suboptimal
A solution is called suboptimal if a part of the solution has been optimized without regards to the overall objective.
 iron intakes.

Maternal dietary calcium and neonatal blood lead are inversely related in the APILS sample. These findings are consistent with results from carefully conducted cross-sectional studies cross-sectional study
n.
See synchronic study.


cross-sectional study,
n the scientific method for the analysis of data gathered from two or more samples at one point in time.
 finding higher calcium intakes related to lower lead levels (Cifuentes et al. 2000; Farias et al. 1996; Goyer 1997; Han et al. 2000; Hernandez-Avila et al. 1996; Hertz-Picciotto et al. 2000; Kostial et al. 1991; Mahaffey et al. 1986; Miller et al. 1990). In a longitudinal study of mother-neonate lead levels in Mexico (Rothenberg et al. 1996), greater maternal milk consumption during pregnancy was associated with lower neonatal lead. Thus, calcium intake appears to be related to lead both at low maternal lead levels, as in the APILS sample, and at higher levels, as in the Mexican sample. Whether the effect of calcium is present across the range of calcium intakes or is confined to mothers with intakes lower than the RDA could not be resolved here because the small size of the APILS sample precluded testing effects in subsamples below or above the RDA for calcium. Hertz-Piccioto and colleagues (2000) found an effect of calcium above the RDA, but other studies have not investigated this or have not found it.

The similar effects of maternal dietary calcium and vitamin D on neonatal lead levels that we observe in the APILS sample are reasonable, given the coincidence of sources of both nutrients in maternal diets (reflected in the high correlation between them). Our results also are consistent with the finding that adjustment for vitamin D levels removes the effect of calcium on blood lead among a sample of mature men (Cheng et al. 1998).

Our results show that calories are positively related to lead level. Insofar in·so·far  
adv.
To such an extent.

Adv. 1. insofar - to the degree or extent that; "insofar as it can be ascertained, the horse lung is comparable to that of man"; "so far as it is reasonably practical he should practice
 as diet serves as a major vehicle for the ingestion ingestion /in·ges·tion/ (-chun) the taking of food, drugs, etc., into the body by mouth.

in·ges·tion
n.
1. The act of taking food and drink into the body by the mouth.

2.
 of lead in the United States, our finding is consistent with calories' being an indicator of dietary quantity. This finding also agrees with several other studies with multivariable analyses that take other nutrients into account (Hammad et al. 1996; Lucas et al. 1996) although it does not agree with all (Mahaffey et al. 1986; Mooty et al. 1975).

Our findings that maternal lead levels during pregnancy are strongly related to neonatal lead level are consonant consonant

Any speech sound characterized by an articulation in which a closure or narrowing of the vocal tract completely or partially blocks the flow of air; also, any letter or symbol representing such a sound.
 with previously published studies (Amitai et al. 1999; Angell and Lavery 1982; Campagna et al. 1999; Carbone et al. 1998; Chuang et al. 2001; Dietrich et al. 1987; Graziano et al. 1990; Lauwerys et al. 1978; McMichael et al. 1988; Nashashibi et al. 1999; Navarrete-Espinosa et al. 2000). The correlation in the APILS sample between maternal and neonatal lead levels at parturition parturition
 or birth or childbirth or labour or delivery

Process of bringing forth a child from the uterus, ending pregnancy. It has three stages.
 is well within the published range from 0.36 (Amitai et al. 1999) to 0.92 (Graziano et al. 1990). The strong relationship between maternal lead levels and ethnicity/race in the APILS sample is consistent with the distribution of lead levels in the United States. Further, this relationship is reflected in the multivariate analyses where ethnicity/race is not significantly related to neonatal lead when maternal lead levels also are in the model. This reflects the difference in lead levels by maternal ethnicity/race. The large impact of maternal blood lead levels points to the need for interventions before pregnancy to reduce lead transmission from mother to offspring.

Managing maternal diets during pregnancy to ensure intakes of calcium, vitamin D, and iron at or above the RDA is warranted by our results. For example, a two-standard-deviation increase in the intake of iron and calcium resulted in a decrease in neonatal blood lead level of 0.77 [micro]g/dL or 45% of the mean neonatal level. A further opportunity for lowering lead levels by adjusting nutrient intakes may occur during infancy, and a future report from this data set will address this problem.
Table 1. Characteristics of mothers at time of study
enrollment (n = 220).

Characteristics                                 Values

Categorical variables, no. (%)
  Ethnicity/race
    African American                           103 (47)
    White                                       71 (32)
    Hispanic                                    32 (15)
    Other                                       14 (6)
  Marital status
    Single                                     157 (71)
    Married                                     42 (19)
    Separated/divorced                          21 (10)
  Currently employed
    (at time of enrollment)
    Yes                                         84 (38)
    No                                         132 (60)
    Not reported                                 4 (2)
  Previously employed
    (preceding 6 months)
    Yes                                        127 (58)
    No                                          89 (41)
    Not reported                                 4 (2)
Continuous variables, mean [+ or -] SD
  Age at enrollment (years)               23.5 [+ or -] 5.49
  Years of education                      11.5 [+ or -] 2.00
  Gravidity                                3.2 [+ or -] 2.18
  Parity                                   1.2 [+ or -] 1.51
  Prepregnancy weight (kg)                68.3 [+ or -] 20.15

Table 2. Geometric mean (GM) of maternal blood lead measurements
during pregnancy and infant's blood lead measurement at birth.

                                     Total sample

Lead ([micro]g/dL)    No.     GM [+ or -] SD      Maximum (a)

Trimester 1            94    1.9 [+ or -] 1.68       12.9
Trimester 2           209    1.8 [+ or -] 1.63       10.4
Trimester 3           198    1.8 [+ or -] 1.65        9.4
Delivery (mother)     211    2.2 [+ or -] 1.72       11.2
Delivery (infant)     220    1.6 [+ or -] 1.78        6.9

                                         Whites

Lead ([micro]g/dL)    No.     GM [+ or -] SD      Maximum (a)

Trimester 1            94    1.6 [+ or -] 1.25        3.8
Trimester 2           209    1.6 [+ or -] 1.65        7.6
Trimester 3           198    1.5 [+ or -] 1.73        3.8
Delivery (mother)     211    1.8 [+ or -] 1.72        5.6
Delivery (infant)     220    1.3 [+ or -] 1.75        4.0

                                   African-Americans

Lead ([micro]g/dL)    No.     GM [+ or -] SD      Maximum (a)

Trimester 1            94    2.2 [+ or -] 1.61        7.5
Trimester 2           209    1.8 [+ or -] 1.62        6.6
Trimester 3           198    2.0 [+ or -] 1.54        7.5
Delivery (mother)     211    2.5 [+ or -] 1.67        8.8
Delivery (infant)     220    1.8 [+ or -] 1.79        6.5

                                Race/ethnicity
Lead ([micro]g/dL)    No.    t-test (p-value) (b)

Trimester 1            94       -3.06 (0.003)
Trimester 2           209       -1.92 (0.056)
Trimester 3           198       -3.86 (< 0.001)
Delivery (mother)     211       -4.13 (< 0.001)
Delivery (infant)     220       -3.18 (0.002)

(a) Not log transformed. (b) t-Test comparing lead levels in
white and African-American subsamples.

Table 3. Relationship of newborn blood lead level to maternal blood
lead levels during pregnancy
(Pearson correlations).

                                          Newborn lead level
                                              at birth

Maternal lead                           Total sample    Whites

Trimester 1
  r                                         0.66          0.46
  p-Value                                 < 0.001         0.006
  No.                                      94            35
Trimester 2
  r                                         0.53          0.53
  p-Value                                 < 0.001       < 0.001
  No.                                     209            66
Trimester 3
  r                                         0.69          0.63
  p-Value                                 < 0.001       < 0.001
  No.                                     198            65
At delivery
  r                                         0.81          0.77
  p-Value                                 < 0.001       < 0.001
  No.                                     211            70
Change: second trimester to delivery
  r                                         0.37          0.32
  p-Value                                 < 0.001       < 0.001
  No.                                     201            65

                                        Newborn lead level
                                             at birth

Maternal lead                           African Americans

Trimester 1
  r                                            0.71
  p-Value                                    < 0.001
  No.                                         45
Trimester 2
  r                                            0.53
  p-Value                                    < 0.001
  No.                                        101
Trimester 3
  r                                            0.67
  p-Value                                    < 0.001
  No.                                         92
At delivery
  r                                            0.81
  p-Value                                    < 0.001
  No.                                         98
Change: second trimester to delivery
  r                                            0.38
  p-Value                                    < 0.001
  No.                                         96

Table 4. Bivariate correlations (Pearson correlation coefficients) of
newborn blood lead concentration at birth to maternal characteristics.

                                            All ethnicities/races
Maternal variable                    No.         r(p-value)

Age                                  220        0.28 (< 0.001)
El                                   220       -0.20 (0.003)
Arm circumference: 2nd trimester     216        0.16 (0.023)
Triceps skinfold: 2nd trimester      216        0.15 (0.033)
Prepregnancy weight                  213        0.16 (0.021)
Prepregnancy BMI                     213        0.19 (0.007)
Maternal weight rate of change:       94       -0.31 (0.002)
  trimesters 1-3
Maternal weight rate of change:      206       -0.32 (< 0.001)
  trimesters 1-3
Maternal arm circ rate of change:     94       -0.21 (0.045)
  trimesters 1-3
Maternal arm circ rate of change:    206       -0.32 (< 0.001)
  trimesters 2-3
                                                 White
Maternal variable                    No.      r(p-value)

Age                                  220     0.25 (0.038)
El                                   220     0.25 (0.038)
Arm circumference: 2nd trimester     216     0.22 (0.077)
Triceps skinfold: 2nd trimester      216     0.03 (0.781)
Prepregnancy weight                  213     0.19 (0.121)
Prepregnancy BMI                     213     0.18 (0.147)
Maternal weight rate of change:       94    -0.32 (0.068)
  trimesters 1-3
Maternal weight rate of change:      206    -0.24 (0.056)
  trimesters 1-3
Maternal arm circ rate of change:     94    -0.22 (0.213)
  trimesters 1-3
Maternal arm circ rate of change:    206    -0.46 (< 0.001)
  trimesters 2-3

                                                Black
Maternal variable                    No.      r(p-value)

Age                                  220     0.33 (0.001)
El                                   220    -0.07 (0.522)
Arm circumference: 2nd trimester     216     0.20 (0.043)
Triceps skinfold: 2nd trimester      216     0.24 (0.014)
Prepregnancy weight                  213     0.16 (0.104)
Prepregnancy BMI                     213     0.21 (0.039)
Maternal weight rate of change:       94    -0.19 (0.210)
  trimesters 1-3
Maternal weight rate of change:      206    -0.38 (< 0.001)
  trimesters 1-3
Maternal arm circ rate of change:     94    -0.22 (0.151)
  trimesters 1-3
Maternal arm circ rate of change:    206    -0.27 (0.007)
  trimesters 2-3

circ, circumference.

Table 5. Average nutritional intakes of women across three trimesters
of pregnancy (n = 83), compared with the 1989 recommended dietary
allowances.

Nutrients             Mean [+ or -] SD        Minimum    Maximum

Calcium (mg)       1180.7 [+ or -] 597.29      267.3     2817.0
Vitamin D (mg)        6.4 [+ or -] 4.02          0.5       21.9
Iron (mg)            21.0 [+ or -] 9.18          6.7       55.6
Zinc (mg)            13.7 [+ or -] 6.09          3.6       34.8
Protein (g)          93.8 [+ or -] 44.45        23.9      272.0
Calories (kcal)    2675.5 [+ or -] 1081.47     917.9     6394.1
Fat (g)              96.6 [+ or -] 43.70        22.0      246.6

                       < RDA

Nutrients          No.    Percent     RDA

Calcium (mg)        50      60       1,200
Vitamin D (mg)      69      83          10
Iron (mg)           69      83          30
Zinc (mg)           57      69          15
Protein (g)         16      19          60
Calories (kcal)     45      54       2,500
Fat (g)

Table 6. Relationship of maternal nutrition, anthropometry, lead
levels, and diet to newborn's blood lead level.

                                            [beta]       [beta]
Terms                                     coefficient      SE

Constant                                   -0.473        0.269
Age                                         0.006        0.004
Education index                             0.095        0.229
Ethnicity/race                             -0.009        0.045
(black = 1, nonblack = 0)
Prepregnancy BMI                            0.008        0.005
Triceps skinfold: second trimester         -0.008        0.004
Arm circ rate of change: trimester 2-3     -2.989        0.888
Lead at delivery ([micro]g/dL)              0.798        0.061
Lead at second trimester ([micro]g/dL)      0.112        0.059
Caloric intake (kcal)                       0.0003       0.0001
Iron intake (mg)                           -0.016        0.008
Calcium intake (mg)                        -0.0001       0.0001
Zinc intake (mg)                           -0.0005       0.012
Fats intake (g)                            -0.002        0.001
Protein intake (g)                          0.0002       0.002

                                          Standardized
Terms                                        [beta]       t-Value

Constant                                                   -1.76
Age                                           0.07          1.35
Education index                               0.02          0.41
Ethnicity/race                               -0.01         -0.20
(black = 1, nonblack = 0)
Prepregnancy BMI                              0.13          1.63
Triceps skinfold: second trimester           -0.17         -2.14
Arm circ rate of change: trimester 2-3       -0.14         -3.37
Lead at delivery ([micro]g/dL)                0.82         13.05
Lead at second trimester ([micro]g/dL)        0.11          1.88
Caloric intake (kcal)                         0.63          3.65
Iron intake (mg)                             -0.30         -2.10
Calcium intake (mg)                          -0.15         -2.08
Zinc intake (mg)                             -0.01         -0.04
Fats intake (g)                              -0.22         -1.78
Protein intake (g)                            0.02          0.13

Terms                                     p-Value

Constant                                   0.083
Age                                        0.183
Education index                            0.680
Ethnicity/race                             0.845
(black = 1, nonblack = 0)
Prepregnancy BMI                           0.109
Triceps skinfold: second trimester         0.036
Arm circ rate of change: trimester 2-3     0.001
Lead at delivery ([micro]g/dL)             0.000
Lead at second trimester ([micro]g/dL)     0.065
Caloric intake (kcal)                      0.001
Iron intake (mg)                           0.040
Calcium intake (mg)                        0.042
Zinc intake (mg)                           0.969
Fats intake (g)                            0.079
Protein intake (g)                         0.897

circ, circumference. Model: r = 0.95, [r.sup.2] = 0.90, n = 83.

Table 7. Relationship of maternal dietary intakes during pregnancy
to newborn's blood lead level: effects of single dietary variables
when added to the core model (a) of control variables.

                                       [beta]
Core model plus single nutrient      coefficient    [beta] SE

Maternal iron intake (mg)              -0.014         0.005
or Maternal zinc intake (mg)           -0.022         0.007
or Maternal vitamin D intake (mg)      -0.014         0.007
or Maternal fats intake (g)            -0.002         0.001
or Maternal protein intake (g)         -0.002         0.001
or Maternal calcium intake (mg)        -0.0001        0.0001

                                     Standardized
Core model plus single nutrient         [beta]       t-Value

Maternal iron intake (mg)               -0.26         -3.06
or Maternal zinc intake (mg)            -0.27         -3.24
or Maternal vitamin D intake (mg)       -0.11         -2.11
or Maternal fats intake (g)             -0.17         -1.41
or Maternal protein intake (g)          -0.22         -1.69
or Maternal calcium intake (mg)         -0.12         -1.73

Core model plus single nutrient      p-Value

Maternal iron intake (mg)             0.003
or Maternal zinc intake (mg)          0.002
or Maternal vitamin D intake (mg)     0.038
or Maternal fats intake (g)           0.162
or Maternal protein intake (g)        0.096
or Maternal calcium intake (mg)       0.088

Core model: r= 0.93, [r.sup.2] = 0.87, n = 83.

(a) The core model controls for age, education index, ethnicity/race,
prepregnancy BMI, second-trimester triceps skinfold, rate of change of
arm circumference from the second to third trimester, and mother's
blood lead at delivery and during the second trimester.


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Lawrence M. Scheft, (1) Melinda Denham, (2) Alice D. Stark, (3) Marta Gomez, (3) Julia Ravenscroft, (2) Patrick J. Parsons, (4) Aida Aydermir, (5) and Renee Samelson (6)

(1) Department of Epidemiology, and (2) Department of Anthropology, University at Albany, State University of New York, Albany, New York For other uses, see Albany.
Albany is the capital of the State of New York and the county seat of Albany County. Albany lies 136 miles (219 km) north of New York City, and slightly to the south of the juncture of the Mohawk and Hudson Rivers.
, USA; (3) Bureau of Environmental and Occupational Epidemiology, New York State Department of Health, Troy, NY, USA; (4) Lead Poisoning/Trace Elements Laboratory Wadsworth Center, New York State Department of Health, Albany, New York, USA; (5) Department of Biostatistics biostatistics /bio·sta·tis·tics/ (-stah-tis´tiks) biometry.

bi·o·sta·tis·tics
n.
The science of statistics applied to the analysis of biological or medical data.
, University at Albany, State University of New York, Albany, New York, USA; (6) Department of Obstetrics and Gynecology obstetrics and gynecology

Medical and surgical specialty concerned with the management of pregnancy and childbirth and with the health of the female reproductive system.
, Albany Medical Center, Albany, NY, USA

Address correspondence to L.M. Schell, A&S 237, University at Albany, State University of New York, 1400 Washington Ave. Albany, NY 12222 USA. Telephone: (518) 442-4714. Fax: (518) 442-4563. E-mail: l.schell@albany.edu

We thank A. Cardemon, J. Crucetti, G. Deane, M. Egolstein, M. Gordon, W.A. Grattan, M. Heigel, M. Schmidt, J. Waldron, P. Weinbaum, M.E. White, and staff at the County of Albany Department of Health and at the Albany Medical College Albany Medical College (AMC) is a medical school located in Albany, New York, United States. It was founded in 1839. The college is part of the Albany Medical Center, which includes the Albany Medical Center Hospital. .

This study was supported by the National Institute of Environmental Health Sciences The National Institute of Environmental Health Sciences (NIEHS) is one of 27 Institutes and Centers of the National Institutes of Health (NIH),which is a component of the Department of Health and Human Services (DHHS). The Director of the NIEHS is Dr. David A. Schwartz.  grant # R01-ES 05280.

Received 11 March 2002; accepted 20 September 2002.
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Author:Samelson, Renee
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Date:Feb 1, 2003
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