Open Access
Open Peer Review

This article has Open Peer Review reports available.

How does Open Peer Review work?

Maternal concentration of polychlorinated biphenyls and dichlorodiphenyl dichlorethylene and birth weight in Michigan fish eaters: a cohort study

Environmental Health20043:1

https://doi.org/10.1186/1476-069X-3-1

Received: 08 December 2003

Accepted: 28 January 2004

Published: 28 January 2004

Abstract

Background

Studies on maternal exposure to polychlorinated biphenyls (PCBs) reported inconsistent findings regarding birth weight: some studies showed no effect, some reported decreased birth weight, and one study found an increase in weights. These studies used different markers of exposure, such as measurement of PCBs in maternal serum or questionnaire data on fish consumption. Additionally maternal exposures, such as dichlorodiphenyl-dichloroethylene (DDE), which are related to PCB exposure and may interfere with the PCB effect, were rarely taken into account.

Methods

Between 1973 and 1991, the Michigan Department of Community Health conducted three surveys to assess PCB and DDE serum concentrations in Michigan anglers. Through telephone interviews with parents, we gathered information on the birth characteristics of their offspring, focusing on deliveries that occurred after 1968. We used the maternal organochlorine (OC) measurement closest to the date of delivery as the exposure. Although one mother may have contributed more than one child, serum concentrations derived from measurements in different surveys could vary for different children from the same mother. The maternal DDE and PCB serum concentrations were categorized as follows: 0 -< 5 microg / L, 5 -< 15 microg / L, 15 -< 25 microg / L, ≥25 microg / L. Using repeated measurement models (Generalized Estimation Equation), we estimated the adjusted mean birth weight controlling for gender, birth order, gestational age, date of delivery as well as maternal age, height, education, and smoking status.

Results

We identified 168 offspring who were born after 1968 and had maternal exposure information. We found a reduced birth weight for the offspring of mothers who had a PCB concentration ≥25 microg / L (adjusted birth weight = 2,958 g, p = 0.022). This group, however, was comprised of only seven observations. The association was not reduced when we excluded preterm deliveries. The birth weight of offspring was increased in women with higher DDE concentrations when controlling for PCBs; however, this association was not statistically significant.

Conclusion

Our results contribute to the body of evidence that high maternal serum PCB concentration may reduce the birth weight in offspring. However, only a small proportion of mothers may actually be exposed to PCB concentrations ≥25 microg / L.

Background

Polychlorinated biphenyls (PCBs) and dichlorodiphenyl-dichloroethylene (DDE) are ubiquitously distributed environmental contaminants. Due to their lipophilic properties and the low rate at which they are metabolized, organochlorine compounds (OC), such as PCBs and DDE, are biomagnified in the food chain and bioaccumulated within individuals [1]. Both PCBs and DDE have long half-lives; for DDE it is longer than seven years; for different PCB congeners their half-live range between 1 and 71 years [25]. PCBs and DDE are capable of crossing the placenta; hence, the developing human fetus of an exposed mother is considered to be at a high risk of being exposed to these compounds [6, 7].

Birth weight is considered to be a predictor of a variety of adverse developments in childhood and beyond, including poor school performance, high blood pressure, cardiovascular disease, and depression [812]. Thus, it is important to assess whether exposure to PCBs and DDE may contribute to reduced birth weight. Investigations of PCB and DDE exposure and birth weight have produced inconsistent results. However, these studies measured exposure differently: some studies determined PCB or DDE concentrations from maternal blood [1318], cord blood [13, 14], placenta [19], or human milk samples [2025]. Others measured exposure using consumption of contaminated fish or cooking oil [13, 2629], place of residence [3032], or type of occupation, as an indicator of toxicant body burden [31, 33].

Of the four studies that investigated regional or occupational exposure categories and PCB exposure, two were based on the frequency of low birth weight (LBW) as the outcome [31, 32] and two compared mean birth weight [30, 33]. Three of these four reports indicated an adverse effect of PCB exposure. Of the five research projects that employed fish consumption or contaminated cooking oil as an indicator of PCB exposure, two found a decreased mean birth weight [13, 29], one a higher frequency of LBW [27], one no association [28], and one an increase in birth weight [26]. A limitation of projects that used aggregative categories to indicate exposure, such as region, occupation, and fish or contaminated cooking oil consumption, is that they cannot disentangle the effects of different organochlorine compounds such as PCBs and DDE. Of the six studies that analyzed breast milk as an approximation of intrauterine exposure to either DDE or PCBs, two found no effects of exposure to DDE or PCBs [21, 24], one no association with PCBs [22], one a higher incidence of low birth weight with PCBs in girls only [20], and two a decreased birth weight related to DDE exposure [23, 25]. In summary, the five exposure approximations above (region, occupation, fish or contaminated cooking oil consumption, and breast milk) reveal conflicting evidence for PCBs: seven studies found an adverse effect, whereas five did not.

Studies that assessed PCB or DDE exposure from maternal, cord blood or placentas have more consistent findings. Four out of five studies on PCBs reported an adverse effect on birth weight [1315, 19]; one did not[16]. Two other studies focused on DDE and reported a decrease in birth weight [17, 18, 23]. In some investigations of organochlorine contaminations, a limitation is focusing solely on one or a group of chemicals (for instance DDE or PCBs). Since we know that in humans the concentrations of different organochlorine compounds are correlated [34, 35], it is possible, that the negative effect attributed to DDE is in fact due to PCBs, or vice versa.

Another line of inquiry has suggested that DDE exerts estrogenic effects, in particular p, p'-DDE [3638]. Maternal estrogens during pregnancy have been shown to increase birth weight [39]. Hence, it is plausible that DDE may increase birth weight. The DDE effect, however, may be missed or masked by a possible opposite effect of PCBs if exposures are not separated in the analysis.

Taking the above considerations into account, we will focus on maternal serum levels and exposures to DDE and PCBs, separately. Our hypotheses are: PCBs decrease birth weight; DDE increases birth weight.

People who consume a diet with a high percentage of fish, such as sport fishermen and their families, are considered to be at greater risk of PCB and DDE exposure compared to the general population for example, people living in the Great Lakes region [4042]. For this reason, fish eaters and their families have been the focus of many environmental and epidemiological studies. For this study we used the Michigan fish eater cohort to test our hypotheses.

Methods

Study Sample

Between 1973 and 1991, the Michigan Department of Community Health conducted three surveys to assess the serum concentration of PCBs and DDE in Michigan anglers (Great Lakes Fish Eater Study, GLFS) as described in several reports [41, 43, 44]. We were interested in potential effects of these toxicants in offspring. It turned out that this cohort of anglers was diverse, including a wide age range and women who never were at risk of child bearing (e.g. nuns). In this work we focus on births that occurred after 1968 in this cohort of anglers. A total of 310 female cohort members were of reproductive age after 1968 (maximum age of 45 years) and had serum organochlorine concentrations determined between 1973 and 1991. In the year 2000, we approached this cohort again. Through telephone interviews, we gathered information on birth characteristics of their offspring, including birth weight. When interviews were scheduled, the subjects were encouraged to have their documents (birth certificates, hospital address, etc.) on hand for the appointed interview.

Additionally, in order to check the reliability of the birth weight information, we compared these parental reports with birth registry data in a subsample of female offspring who participated in an additional follow-up study. In the second generation follow-up (proportion of participation: 75%), we had 49 female offspring born after 1968, among them 42 allowed us to access their vital statistic records. The study was approved by the boards reviewing research on human subjects at Michigan State University and the Michigan Department of Community Health.

PCB and DDE determination

PCB was determined in all three surveys (1973 – 1974, 1979 – 1982, 1989 – 1991), while DDE was determined in the second and third. To compare exposures, we used those PCBs measurements based on the Aroclor 1260 standard, which measured the more highly PCB chlorinated congeners. Analyses of serum specimens were performed by the Michigan Department of Community Health (Webb-McCall packed column gas chromatography technique). The technical detection limit for PCBs was 3 μg / L and 1 μg / L for DDE.

Statistical analysis

Birth weight was the primary outcome in our study. Although one mother may have more than one child, exposure could vary for different children from the same mother. We used the measurement that was closest to the date of delivery as the maternal exposure. When investigating exposure-response relationships, there are several choices how to deal with exposure data. One is to rely on a continuous exposure. This is appropriate if there is a simple linear exposure-response relationship. A second choice is to group exposure according to their frequency into quartiles, quintiles, etc. The risk of this approach, however, is that having a skewed distribution may result in fewer higher exposures being pooled with medium levels, increasing the likelihood that adverse effects of higher exposure are masked. Another problem with using quartiles is the lack of equidistant categories. A third option is to categorize exposure levels into equidistant groups that can also facilitate addressing a potential adverse effect of higher level and a threshold effect. Since prior data showed a threshold effect for higher organochlorine levels [17, 18, 23], we decided to categorized maternal DDE and PCB serum concentrations as follows: 0 -< 5 μg / L, 5 -< 15 μg / L, 15 -< 25 μg / L, ≥25 μg / L. Since linearity between gestational age (in weeks) and birth weight was confirmed, we chose to use gestational age as a continuous variable. For descriptive purposes, we divided it into three categories: < 37 weeks, 37 -< 40 weeks, and ≥40 weeks. Three maternal-age groups represent women 15 – 24, 25 – 29 and > 29 years of age at the time of delivery. Educational level of the women, collected from the 1989 – 1991 GLFS questionnaires, was divided into three categories: high school or less, some college, and college graduate or higher. Since maternal height may explain birth weight [45], we also included maternal height as a confounder in the analysis. We obtained smoking status from the 1989 – 1991 GLFS questionnaire. If pregnancy occurred within the time a woman reported having smoked, we recorded smoking status as affirmative. We also included the child's year of birth to assess whether a birth cohort effect might explain different birth weight (categories were 1968 – 1972, 1973 – 1983, and after 1983).

We applied a repeated measurements model to adjust for the autocorrelation of birth weight between siblings from the same mother. Using Generalized Estimation Equations (GEE, SAS PROC MIXED) [46], we estimated the adjusted mean birth weight controlling for gender, birth order, gestational age, date of delivery as well as maternal age, height, education, and smoking status. In our repeated measurements model we treated gender, birth order, date of delivery as well as maternal age, education, and smoking status as categorical variables, while both gestational age and maternal height were treated as continuous variables.

Results

Of the Great Lakes Fish Eater Study cohort, 310 women were 45 years or younger in 1968 and could potentially give birth to a child. In the year 2000, of the 310 women, three were deceased, 73 could not be contacted, and eight did not consent to participate. With 226 women who give their consent, the proportion of participation is 72.9% (226/310). Of the 226 women, 99 gave birth between 1969 and 1995, resulting in a total of 195 offspring. Since twins usually have lower birth weight than singletons, we excluded four pairs of twins (n = 8) from our data, as well as 19 newborns with missing values for birth weight (n = 10) or educational status of the mother (n = 9). Hence, our analysis is based on 168 offspring who came from 89 mothers. Among the 168 offspring, 47.6% were boys; 28.6% were born between 1968 and 1972; 58.3% were born between 1973 and 1983; and 13.1% after 1983 (Table 1). A maternal DDE exposure equal to or larger than 25 μg / L or PCB exposure equal to or larger than 25 μg / L occurred only in a few observations (eight and seven offspring, respectively).
Table 1

Description of the study population

Characteristic

 

n = 168

%

Gender

Male

80

47.6

 

Female

88

52.4

Maternal DDE (μg / L)

< 5

46

27.4

 

5 -< 15

89

53.0

 

15 -< 25

25

14.9

 

≥25

8

4.7

Maternal PCB (μg / L)

< 5

84

50.0

 

5 -< 15

66

39.3

 

15 -< 25

11

6.5

 

≥25

7

4.2

Parity

0

57

33.9

 

1

65

38.7

 

2

31

18.5

 

≥3

15

8.9

Gestational age (weeks)

< 37

5

3.0

 

37 -< 40

23

13.7

 

≥40

140

83.3

Maternal age (years)

15 – 24

41

24.4

 

25 – 29

70

41.7

 

30 and older

57

33.9

Maternal height (cm)

<155

14

8.3

 

155 -< 170

122

72.6

 

≥170

32

19.1

Maternal education

High school

71

42.3

 

College

44

26.2

 

College plus

53

31.5

Maternal smoking status during pregnancy

Yes

22

13.1

 

No

146

86.9

Child birth year

1968 – 1972

48

28.6

 

1973 – 1982

98

58.3

 

>1983

22

13.1

The proportion of boys increased with increasing organochlorine levels (Table 2), which has been reported before for this sample regarding paternal exposure [47]. Maternal age at delivery was not significantly different between exposure groups. We found that maternal PCB levels were significantly higher in children born at an earlier calendar period (between 1969 – 1972, Table 2). A higher DDE exposure was obvious for children born between 1973 and 1982.
Table 2

Relationship between PCB, DDE, and potential confounders

 

Exposure category

n

Boys (%)

Parity at before delivery (mean)

Gestational age (mean)

Maternal age at delivery (mean)

Maternal Height (mean)

Maternal education (%)

Maternal smoking during pregnancy (%)

Child birth year (%)

        

High school

College

College and higher

 

69-<73

73-< 83

> 83

Maternal DDE (μg / L)

< 5

46

39.1

0.9

39.8

27.6

163.4

34.8

32.6

32.6

2.2

17.4

58.7

23.9

 

5 -< 15

89

48.3

1.0

39.9

28.0

163.9

45.0

15.7

39.3

15.7

24.7

62.9

12.4

 

15 -< 25

25

56.0

1.3

40.2

27.6

165.6

44.0

44.0

12.0

20.0

60.0

40.0

0

 

≥ 25

8

62.5

0.9

40.5

29.0

166.4

50.0

50.0

0

25.0

37.5

62.5

0

Maternal PCB (μg / L)

< 5

84

45.2

1.0

40.1

28.0

163.6

32.2

33.3

34.5

13.1

16.7

61.9

21.4

 

5 -< 15

66

48.5

0.9

39.9

27.9

163.9

51.5

13.6

34.9

16.7

30.3

63.6

6.1

 

15 -< 25

11

36.4

1.3

39.6

27.3

166.3

72.7

27.3

0

0

63.6

36.4

0

 

≥ 25

7

85.7

1.9

40.0

27.9

169.1

28.6

57.1

14.3

0

100

0

0

Crude birth weight and adjusted birth weight estimated through linear regression analyses are presented in Table 3. The results show that boys were heavier at birth; birth weight increased with gestational age; and there was a significant increase in birth weight with birth order. We did not detect a statistically significant difference in birth weight for different level of exposure to DDE (Table 3). However, the birth weight of the offspring of mothers who had the highest PCB levels (≥ 25 μg / L) significantly reduced by approximately 500 g (p = 0.022) (Table 3). When stratified for gender, PCB exposure was associated with a reduced birth weight in males only. The reduction in boys in the highest PCB exposure level was 561 g (p = 0.02) and 241 g in girls (p = 0.66), however, there was only one girl and six boys in the highest PCB exposure group (≥ 25 μg / L serum).
Table 3

Birth weight in grams in different subgroups

Characteristic

 

n = 168

Crude birth weight in g (5 – 95% values)

Adjusted ψ birth weight in g (5 – 95% values)

Gender

Male

80

3536 (2679 – 4380)

3491 (3283 – 3698)*

 

Female

88

3385 (2693 – 4167)

3272 (3062 – 3481)

Maternal DDE (μg / L)

< 5

46

3411 (2693 – 4139)

3278 (2979 – 3577)

 

5 -< 15

89

2456 (2637 – 4253)

3365 (3130 – 3600)

 

15 -< 25

25

3504 (2722 – 4253)

3440 (3198 – 3685)

 

≥ 25

8

3572 (2807 – 4338)

3278 (3065 – 3815)

Maternal PCB (μg / L)

< 5

84

3470 (2693 – 4338)

3520 (3318 – 3723)

 

5 -< 15

66

3428 (2608 – 4167)

3509 (3312 – 3707)

 

15 -< 25

11

3647 (3033 – 4167)

3537 (3137 – 3937)

 

≥ 25

7

3268 (2722 – 4338)

2958 (2519 – 3397)*

Parity

0

57

3345 (2552 – 4139)

3211 (2999 – 3423)*

 

1

65

3474 (2722 – 4253)

3378 (3169 – 3587)

 

2

31

3523 (2722 – 4763)

3401 (3168 – 3633)

 

≥ 3

15

3668 (3289 – 4338)

3535 (3246 – 3824)

Gestational age

< 37

5

2427 (1361 – 3033)

Continuous variable*

 

37 -< 40

23

3279 (2693 – 3941)

 
 

≥ 40

140

3522 (2792 – 4309)

 

Maternal age (years)

15 – 24

41

3388 (2892 – 4082)

3414 (3158 – 3669)

 

25 – 29

70

3517 (2693 – 4309)

3396 (3181 – 3610)

 

30 and older

57

3432 (2580 – 4536)

3334 (3128 – 3541)

Maternal height (cm)

< 155

14

3112 (2552 – 3714)

Continuous variable

 

155 -< 170

122

3470 (2693 – 4167)

 
 

≥ 170

32

3555 (2722 – 4536)

 

Maternal education

High school

71

3379 (2693 – 4139)

3303 (3083 – 3523)

 

College

44

3569 (2722 – 4423)

3433 (3196 – 3670)

 

College plus

53

3467 (2608 – 4309)

3407 (3152 – 3662)

Maternal smoking status during pregnancy

Yes

22

3175 (2552 – 3969)

3294 (3007 – 3581)

 

No

146

3499 (2722 – 4253)

3468 (3300 – 3636)

Child birth year

1968 – 1972

48

3554 (2722 – 4253)

3406 (3200 – 3612)

 

1973 – 1982

98

3420 (2693 – 4253)

3333 (3125 – 3540)

 

> 1983

22

3405 (2608 – 4536)

3405 (3120 – 3689)

* p-value < 0.05 ψ Adjusted for all other variables in Table 3

In addition to controlling for gestational age in the analysis, we determined the percentages of newborns who were considered to be small for gestational age using 10%-reference values [48]. We did not find an association of DDE nor PCB with the prevalence of small for gestational age (average proportion: 8.3%). Finally, when we excluded neonates born before the 37th week of gestation the PCB estimate did not change substantially (reduction of 578 g, p = 0.023). Thus, the association between PCB and birth weight cannot be attributed to preterm delivery.

As these findings include repeated pregnancies from the same women (168 offspring of 89 mothers), we used Generalized Estimation Equations and adjusted for the within-mother effect. To additionally investigate whether the PCB-related reduction in birth weight is also detected when only considering one offspring per mother, we analyzed data for the first offspring born after 1968 (n = 89). The birth weight was reduced in women with PCB serum concentration of 15 -< 25 μg / L by 220 g (p = 0.38) and for PCB ≥ 25 μg / L by 351 g (p = 0.16).

From the 168 offspring, we selected a subsample of 42 adult daughters and obtained permission to access their birth registry data. To check reliability, we compared this information with maternal recall data. For birth weight, agreement between maternal reports and registry information was nearly perfect: the Spearman correlation coefficient (rS) is 0.97 (p = 0.0001).

Discussion

Our study found no significant increase in birth weight associated with maternal DDE exposure, but a significant reduction in birth weight of approximately 500 g in offspring of mothers with PCB levels of ≥ 25 μg / L. However, the group with the highest PCB exposure comprised only seven infants. The association was not reduced when we excluded preterm deliveries.

Of the 310 women in the fish eater cohort who were of childbearing age (maximum age of 45 years), 72.9% participated in the study (n = 226). Since the participation proportion is high, we do not suspect that a selection bias can explain our findings. The fact that only 99 of the participating women gave birth after 1968 is likely to be a reflection of chance and not selection.

Regarding a potential information bias, we had a long recall period between births occurring after 1968 and parental reports on birth weight from interviews in the year 2000. The median recall was 24 years. To check reliability, we compared parental information with birth registry data. For birth weight, the agreement between maternal reports and registry information was nearly perfect (rS = 0.97). We believe that this agreement was achieved primarily due to the fact that most subjects had relevant documents on hand for their interviews. Hence, in accordance with other studies the long recall did not weaken the reliability of the birth weight information [4951].

Regarding smoking during pregnancy as a potential confounder, we cannot exclude the possibility that some women stopped or reduced smoking during pregnancy. However, the crude smoking effect resulted in an expected reduction of approximately 300 g (3,175 g vs. 3499 g, Table 3). To exclude a misclassification of the smoking status differential with regard to exposure, we investigated non-smoking mothers. This group consisted of 22 women who never smoked or stopped smoking in the year prior to conception. The PCB exposure levels for this group were low as documented in Table 2. Eleven women were in the PCB < 5 μg / L class and 11 women were in the 5 -< 15 μg / L PCB exposure class. The respective average birth weights were 3,348 g and 3003 g. Hence, we also see a reduction in birth weight in the non-smoking group associated with the PCB exposure, which makes differential confounding unlikely.

PCB serum concentrations in other studies that focused on maternal blood, cord blood, or placentas overall ranges between 0.08 – 47.73 μg / L: Fein et al. 1984: 5 – 13 μ/L; Sunahara et al. 1987: 2.29 – 47.73 μg / L; Patandin et al. 1998: 0.59 – 7.35 μg / L; Rylander et al. 1998: 0.08 – 4.3 μg / L; a higher exposed group having a serum concentration of more than 11.7 μg / L (assuming a lipid concentration of 9 g / L), Grandjean et al. 2001 [1316, 19]. The serum concentrations of PCBs determined in our study were between 0 and 29 μg / L and exceeded the concentrations found in four of the five previous studies that used maternal or cord blood serum concentrations.

Fein et al. and Patandin et al. have demonstrated a dose-effect relationship for birth weight with consumption of PCB contaminated fish and with PCB concentrations in cord serum, respectively [13, 14]. Our results may indicate a threshold effect, since there is no discernible decrease in birth weight below a maternal PCB concentration of less than 25 μg / L. Assuming an endocrine mode of interference of PCB, a threshold effect is plausible since PCB may hamper the binding of hormones to their receptors [52]. It is possible that the location of the threshold level depends upon smoking, nutrients in fish, and other confounders. Regarding fatty acid intake due to fish consumption, Grandjean et al. reported that some fatty acids, in particular docosapentaenoic acid (DPA), increases birth weight [16]. However, this scenario seems to be even more complex, since the level of DPA also decreases with higher PCB concentrations [16].

Most previous studies that determined organochlorine concentrations in human specimens focused on one compound, for instance PCBs, without considering other correlated toxicants, such as DDE, which might have a confounding effect. In our sample of neonates, maternal PCB and DDE values are correlated (rS = 0.69, p = 0.0001). Thus, we investigated whether the PCB-birth weight association would change if we do not control for DDE. Without having DDE in the regression model, the highest PCB level still has a diminishing effect on birth weight (p = 0.027, 470 g).

One strength of our study is that we used the maternal blood PCB and DDE concentrations, representing direct measurement of organochlorine compounds (OC) and not approximations, such as fish consumptions, as the indicator of intrauterine exposure. Secondly, we included both PCBs and DDE in our final model, which allowed us to explore the effects of PCBs and DDE on birth weight. A limitation, however, is that the OC measurements between 1973 and 1991 do not coincide with the dates of the pregnancies under consideration (> 1968 to 1995). The median difference is five years. Therefore, these values do not directly reflect the OC concentrations to which these offspring were exposed in utero. As expected with persistent chemicals, on average these OC concentrations did not vary much in women when repeated measurements were compared. He et al. analyzed the Michigan fish eater data and reported no substantial decline in the median PCB serum concentration in female fish eaters over three cross-sections (11.0 μg / L in 1973/74; 14.5 μg / L in 1979/82; 13.5 μg / L in 1989/93) [44]. We suppose that chronic consumption of PCB contaminated fish and the long half-lives of PCBs are likely to explain the stability of the serum concentrations. Additionally, we investigated whether PCBs and DDE values were lower, when the spacing between phlebotomy and birth of the child were longer; we found no large differences. For instance PCB levels were higher in both ends of the spacing distribution: 0 – 1 year: 5.4 μg / L, n = 39; 2 – 4 years: 4.0 μg / L, n = 41; 5 – 9 years: 5.2 μg / L, n = 47; > 9 years: 6.1 μg / L, n = 41.

To estimate maternal levels of organochlorine compounds (OC) at the times of pregnancy between 1950 and 1980, we used three repeated serum measurements and additional survey information (1973 – 1974, 1979 – 1982, and 1989 – 1991) [Karmaus W. et al. Unpublished data]. Two linear regression analyses were conducted and their results used to backward extrapolate serum levels. Each of the two regression models covers one period between two of the three survey measurements. We estimated regression coefficients for the most parsimonious models, and tested how well the two equations predicted the actual serum OC concentrations measured in the past. By means of intraclass correlation coefficients (ICC), we compared estimated and measured past concentrations [53]. We identified two formulas that predicted past values with high reliability (ICC = 0.77 for the period of 1991 to 1979, and ICC = 0.89 for the period of 1982 to 1973). The first formula used the PCB values determined in 1989/91, the years that passed between the 1989/91 and 1979/82 determinations, and the number of births in that interval. Of note is that the predicted values were higher in the 1979/82 measurements, as indicated by a positive sign for the years that passed between 1989/91 and 1979/82. The second formula estimates the PCB values in 1973/74 using the 1979/82 determination, the years between 1973/74 and 1979/82, and the years of fish consumption. This formula has a negative sign for the years passed between the two determinations, which indicates lower PCB values for 1979/1982 and before. We applied these formulas to backward-estimate both the maternal serum PCB and DDE concentrations at the time of each pregnancy. When using the values derived from backward extrapolations, our results did not change substantially. The reason is that the ranking of the exposure concentrations changed only marginally when these estimates were used.

A limitation is the lack of information about individual PCB congeners and the lack of information about hydroxylated PCBs. We had to use the total PCB concentration based on the Aroclor 1260 standard. This may be a problem because various PCB congeners may have different, sometimes antagonistic endocrine effects [54, 55]. It has also been reported that hydroxylated PCBs are estrogenic while non-hydroxylated PCBs are not [3638]. An additional limitation is that OC determinations used in our study were determined on a whole serum basis without determination of serum lipids. Thus, we could not determine lipid-based PCB concentrations. However, another strength of the Michigan cohort is that the analytical procedure to determine DDE and PCB (Webb-McCall packed column gas chromatography technique) has not been changed between 1973 and 1991 [43]. These stable analytical techniques facilitated comparisons between PCB and DDE assessment in the three surveys as recently emphasized by Longnecker et al., when comparing different techniques [56].

Several studies have investigated a potential association between PCB and/or DDE exposure and birth weight. However, there is inconsistency when comparing results of studies with varying exposure measurements, which may lead to exposure misclassification. For instance, studies which rely on measurements in breast milk may be plagued by declining OC concentrations with increasing duration of breastfeeding [57], particularly, if the concentration was derived at different times for different participants. However, there is little uncertainty when exposure is determined from maternal or cord blood. Four out of five studies reported an adverse effect on birth weights [1315, 19], one did not [16]. Our study adds to the evidence that high maternal PCB serum concentrations are associated with reduced birth weight. We assume that the apparent inconsistencies in earlier studies can be reduced if the exposure is assessed without major impact of misclassification; for instance, by using maternal or cord blood concentrations. Although we have found that PCBs may be associated with reduced birth weight, the underlying mechanisms remain unknown. We did not have any information on fatty acid in fish or in the female fish eaters. We believe that future studies should also determine phospholipid fatty acids in fish eating populations. Phospholipid fatty acids are provided by seafood and may be beneficial for the pregnancy and offspring [16]. Since both phospholipid fatty acids and OCs have the same origin and thus are highly likely to be correlated, these substances may confound the PCB – birth weight association. However, since the concentrations of some fatty acids are altered by PCBs [16], it may not be the confounding but the intervening effects of phospholipid fatty acids that need to be considered in structural equation models to appropriately estimate the direct and indirect effect (via fatty acid) of PCBs.

Conclusion

Our study adds to existing evidence that in utero exposure to PCB may reduce birth weight when exposure was determined from maternal or cord blood samples. Birth weight is a marker of adverse effects in utero, and/or a predictor of a series of adverse developments in childhood. Future studies are warranted to investigate the potential adverse effects of historic organochlorine compounds such as PCBs and DDE, as well as newly emerging toxicants such as polybrominated diphenylethers on birth weight. We recommend designing future studies in a way that would allow for the discovery of the underlying mechanism.

Abbreviations

PCBs

Polychlorinated Biphenyls

DDE

Dichlorodiphenyl Dichloroethylene

OC

Organochlorine compounds

LBW

Low Birth Weight

GLFS

Great Lakes Fish Eater Study

GEE

Generalized Estimation Equations

ICC

Intra class correlation coefficient

r S

Spearman correlation coefficient

Declarations

Acknowledgement

This work was supported by a grant from the Agency for Toxic substances and Disease Registry (grant number-H75/ATH82536-06). We gratefully thank all participants of the Michigan Great Lakes Fish Eater Study. We are indebted to Susan Davis, Kevin Brooks, Christopher Fussman, and Alireza Sadeghnejad for improvements to the manuscript.

Authors’ Affiliations

(1)
Department of Epidemiology, Michigan State University

References

  1. van der Ven K, van der Ven H, Thibold A, Bauer O, Kaisi M, Mbura J, Mgaya HN, Weber N, Diedrich K, Krebs D: Chlorinated hydrocarbon content of fetal and maternal body tissues and fluids in full term pregnant women: a comparison of Germany versus Tanzania. Hum Reprod. 1992, 7 Suppl 1: 95-100.View ArticleGoogle Scholar
  2. Longnecker MP, Rogan WJ, Lucier G: The human health effects of DDT (dichlorodiphenyltrichloroethane) and PCBS (polychlorinated biphenyls) and an overview of organochlorines in public health. Annu Rev Public Health. 1997, 18: 211-244. 10.1146/annurev.publhealth.18.1.211.View ArticleGoogle Scholar
  3. Phillips Dl, Smith AB, Burse VW, Steele GK, Needham L, Hannon WH: Half-life of polychlorinated biphenyls in occupationally exposed workers. Arch Environ Health. 1989, 44: 351-354.View ArticleGoogle Scholar
  4. Shirai JH, Kissel JC: Uncertainty in estimated half-lives of polychlorinated biphenylin humans: impact on exposure assessment. Sci Total Environ. 1996, 187: 199-210. 10.1016/0048-9697(96)05142-X.View ArticleGoogle Scholar
  5. Yakushiji T, Watanabe I, Kuwabara K, Tanaka R, Kashimoto T, Kunita N: Rate of decrease and half-life of polychlorinated biphenyls (PCBs) in the blood of mothers and their children occupationally exposed to PCBs. Arch Environ Contam Toxicol. 1984, 13: 341-345. 10.1007/BF01055285.View ArticleGoogle Scholar
  6. Covaci A Jorens P, Jacquemyn Y, Schepens P.: Distribution of PCBs and organochlorine pesticides in umbilical cord and maternal serum. Sci Total Environ. 2002, 1-3: 45-53. 10.1016/S0048-9697(02)00167-5.View ArticleGoogle Scholar
  7. Jacobson JL, Fein GG, Jacobson SW, Schwartz PM, Dowler JK: The transfer of polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs) across the human placenta and into maternal milk. Am J Public Health. 1984, 74: 378-379.View ArticleGoogle Scholar
  8. Weindrich D, Jennen-Steinmetz C, Laucht M, Schmidt MH: Late sequelae of low birthweight: mediators of poor school performance at 11 years. Dev Med Child Neurol. 2003, 45: 463-469. 10.1017/S0012162203000860.View ArticleGoogle Scholar
  9. Law CM, Shiell AW, Newsome CA, Syddall HE, Shinebourne EA, Fayers PM, Martyn CN, de Swiet M: Fetal, infant, and childhood growth and adult blood pressure: a longitudinal study from birth to 22 years of age. Circulation. 2002, 105: 1088-1092. 10.1161/hc0902.104677.View ArticleGoogle Scholar
  10. Barker DJ: Fetal programming of coronary heart disease. Trends Endocrinol Metab. 2002, 13: 364-368. 10.1016/S1043-2760(02)00689-6.View ArticleGoogle Scholar
  11. Barker DJ: In utero programming of chronic disease. Clin Sci (Lond). 1998, 95: 115-128. 10.1042/CS19980019.View ArticleGoogle Scholar
  12. Thompson C, Syddall H, Rodin I, Osmond C, Barker DJ: Birth weight and the risk of depressive disorder in late life. Br J Psychiatry. 2001, 179: 450-455. 10.1192/bjp.179.5.450.View ArticleGoogle Scholar
  13. Fein GG, Jacobson JL, Jacobson SW, Schwartz PM, Dowler JK: Prenatal exposure to polychlorinated biphenyls: effects on birth size and gestational age. J Pediatr. 1984, 105: 315-320.View ArticleGoogle Scholar
  14. Patandin S, Koopman-Esseboom C, de Ridder MA, Weisglas-Kuperus N, Sauer PJ: Effects of environmental exposure to polychlorinated biphenyls and dioxins on birth size and growth in Dutch children. Pediatr Res. 1998, 44: 538-545.View ArticleGoogle Scholar
  15. Rylander L, Stromberg U, Dyremark E, Ostman C, Nilsson-Ehle P, Hagmar L: Polychlorinated biphenyls in blood plasma among Swedish female fish consumers in relation to low birth weight. Am J Epidemiol. 1998, 147: 493-502.View ArticleGoogle Scholar
  16. Grandjean P, Bjerve KS, Weihe P, Steuerwald U: Birthweight in a fishing community: significance of essential fatty acids and marine food contaminants. Int J Epidemiol. 2001, 30: 1272-1278. 10.1093/ije/30.6.1272.View ArticleGoogle Scholar
  17. Longnecker MP, Klebanoff MA, Zhou H, Brock JW: Association between maternal serum concentration of the DDT metabolite DDE and preterm and small-for-gestational-age babies at birth. Lancet. 2001, 358: 110-114. 10.1016/S0140-6736(01)05329-6.View ArticleGoogle Scholar
  18. Siddiqui J, Srivastava S, Srivastava P, Mehrotra K, Mathur N, Tandon I: Persistent chlorinated pesticides and intra-uterine foetal growth retardation: a possible association. Int Arch Occup Environ Health. 2003, 76: 75-80.Google Scholar
  19. Sunahara GI, Nelson KG, Wong TK, Lucier GW: Decreased human birth weights after in utero exposure to PCBs and PCDFs are associated with decreased placental EGF-stimulated receptor autophosphorylation capacity. Mol Pharmacol. 1987, 32: 572-578.Google Scholar
  20. Yamashita F, Hayashi M: Fetal PCB syndrome: clinical features, intrauterine growth retardation and possible alteration in calcium metabolism. Environ Health Perspect. 1985, 59: 41-45.View ArticleGoogle Scholar
  21. Rogan WJ, Gladen BC, McKinney JD, Carreras N, Hardy P, Thullen J, Tinglestad J, Tully M: Neonatal effects of transplacental exposure to PCBs and DDE. J Pediatr. 1986, 109: 335-341.View ArticleGoogle Scholar
  22. Vartiainen T, Jaakkola JJ, Saarikoski S, Tuomisto J: Birth weight and sex of children and the correlation to the body burden of PCDDs/PCDFs and PCBs of the mother. Environ Health Perspect. 1998, 106: 61-66.View ArticleGoogle Scholar
  23. Siddiqui MK, Nigam U, Srivastava S, Tejeshwar DS, Chandrawati: Association of maternal blood pressure and hemoglobin level with organochlorines in human milk. Hum Exp Toxicol. 2002, 21: 1-6. 10.1191/0960327102ht198oa.View ArticleGoogle Scholar
  24. Gladen BC, Shkiryak-Nyzhnyk ZA, Chyslovska N, Zadorozhnaja TD, Little RE: Persistent organochlorine compounds and birth weight. Ann Epidemiol. 2003, 13: 151-157. 10.1016/S1047-2797(02)00268-5.View ArticleGoogle Scholar
  25. Polder A, Odland JO, Tkachev A, Foreid S, Savinova TN, Skaare JU: Geographic variation of chlorinated pesticides, toxaphenes and PCBs in human milk from sub-arctic and arctic locations in Russia. Sci Total Environ. 2003, 306: 179-195. 10.1016/S0048-9697(02)00492-8.View ArticleGoogle Scholar
  26. Dar E, Kanarek MS, Anderson HA, Sonzogni WC: Fish consumption and reproductive outcomes in Green Bay, Wisconsin. Environ Res. 1992, 59: 189-201.View ArticleGoogle Scholar
  27. Rylander L, Stromberg U, Hagmar L: Dietary intake of fish contaminated with persistent organochlorine compounds in relation to low birthweight. Scand J Work Environ Health. 1996, 22: 260-266.View ArticleGoogle Scholar
  28. Buck GM Tee GP, Fitzgerald EF, Vena JE, Weiner JM, Swanson M, Msall ME.: Maternal Fish Consumption and Infant Birth Size and Gestation: New York State Angler Cohort Study. Environ Health. 2003, 2: 7-10.1186/1476-069X-2-7.View ArticleGoogle Scholar
  29. Lan SJ, Yen YY, Yang CH, Yang CY, Chen ER: A study on the birth weight of transplacental Yu-Cheng babies. Kao Hsiung I Hsueh Ko Hsueh Tsa Chih. 1987, 3: 273-282.Google Scholar
  30. Taylor PR, Stelma JM, Lawrence CE: The relation of polychlorinated biphenyls to birth weight and gestational age in the offspring of occupationally exposed mothers. Am J Epidemiol. 1989, 129: 395-406.Google Scholar
  31. Rylander L, Stromberg U, Hagmar L: Decreased birthweight among infants born to women with a high dietary intake of fish contaminated with persistent organochlorine compounds. Scand J Work Environ Health. 1995, 21: 368-375.View ArticleGoogle Scholar
  32. Baibergenova A, Kudyakov R, Zdeb M, Carpenter DO: Low birth weight and residential proximity to PCB-contaminated waste sites. Environ Health Perspect. 2003, 111: 1352-1357.View ArticleGoogle Scholar
  33. Taylor PR, Lawrence CE, Hwang HL, Paulson AS: Polychlorinated biphenyls: influence on birthweight and gestation. Am J Public Health. 1984, 74: 1153-1154.View ArticleGoogle Scholar
  34. Karmaus W DeKoning EP, Kruse H, Witten J, Osius N.: Early childhooddeterminants of organochlorine concentrations in school- aged children. Pediatr Res. 2001, 50: 331-336.View ArticleGoogle Scholar
  35. Karmaus W Huang S, Cameron L.: Parental concentration of dichlorodiphenyldichloroethene and polychlorinated biphenyls in Michigan fish eaters and sexratio in offspring. J Occup Environ Med. 2002, 44: 8-13. 10.1097/00043764-200201000-00003.View ArticleGoogle Scholar
  36. You L, Sar M, Bartolucci E, Ploch S, Whitt M: Induction of hepatic aromatase by p,p'-DDE in adult male rats. Mol Cell Endocrinol. 2001, 178: 207-214. 10.1016/S0303-7207(01)00445-2.View ArticleGoogle Scholar
  37. Kurihara N: Chlorinated hydrocarbon insecticides(DDT, methoxychlor, HCH etc.). Nippon Rinsho. 2000, 58: 2417-2421.Google Scholar
  38. Sonnenschein C, Soto AM: An updated review of environmental estrogen and androgen mimics and antagonists. J Steroid Biochem Mol Biol. 1998, 65: 143-150. 10.1016/S0960-0760(98)00027-2.View ArticleGoogle Scholar
  39. Kaijser M, Granath F, Jacobsen G, Cnattingius S, Ekbom A: Maternal pregnancy estriol levels in relation to anamnestic and fetal anthropometric data. Epidemiology. 2000, 11: 315-319. 10.1097/00001648-200005000-00015.View ArticleGoogle Scholar
  40. Swain WR: Effects of organochlorine chemicals on the reproductive outcome of humans who consumed contaminated Great Lakes fish: an epidemiologic consideration. J Toxicol Environ Health. 1991, 33: 587-639.View ArticleGoogle Scholar
  41. Humphrey HEB: Population studies of PCBs in Michigan residents. PCBs: Human and Environmental Hazards. Edited by: D'Itri F M and Kamrin M A. 1983, Boston, Butterworth Publishers, 299-310.Google Scholar
  42. Schantz PM Jacobson SW, Fein G, Jacobson SL, and Price HA: Lake Michigan fish consumption as a source of polychlorinated biphenyls in human cord serum, maternal serum and milk. Am. J. Public Health. 1983, 73: 293-296.View ArticleGoogle Scholar
  43. Humphrey HE, Budd ML: Michigan's fisheater cohorts: a prospective history of exposure. Toxicol Ind Health. 1996, 12: 499-505.View ArticleGoogle Scholar
  44. He JP, Stein AD, Humphrey HE, Paneth N, Courval JM: Time trends in sport-caught Great Lakes fish consumption and serum polychlorinated biphenyl levels among Michigan Anglers, 1973-1993. Environ Sci Technol. 2001, 35: 435-440. 10.1021/es001067p.View ArticleGoogle Scholar
  45. Meis PJ, Michielutte R, Peters TJ, Wells HB, Sands RE, Coles EC, Johns KA: Factors associated with term low birthweight in Cardiff, Wales. Paediatr Perinat Epidemiol. 1997, 11: 287-297.View ArticleGoogle Scholar
  46. SAS Institute: SAS/STAT Software. 2001, Cary, NC, SAS Institute Inc., Version 8.02Google Scholar
  47. Karmaus W, Huang S, Cameron L: Parental concentration of dichlorodiphenyl dichloroethene and polychlorinated biphenyls in Michigan fish eaters and sex ratio in offspring. J Occup Environ Med. 2002, 44: 8-13. 10.1097/00043764-200201000-00003.View ArticleGoogle Scholar
  48. Thomas P, Peabody J, Turnier V, Clark RH: A new look at intrauterine growth and the impact of race, altitude, and gender. Pediatrics. 2000, 106: E21-10.1542/peds.106.2.e21.View ArticleGoogle Scholar
  49. Troy LM, Michels KB, Hunter DJ, Spiegelman D, Manson JE, Colditz GA, Stampfer MJ, Willett WC: Self-reported birthweight and history of having been breastfed among younger women: an assessment of validity. Int J Epidemiol. 1996, 25: 122-127.View ArticleGoogle Scholar
  50. Walton KA, Murray LJ, Gallagher AM, Cran GW, Savage MJ, Boreham C: Parental recall of birthweight: a good proxy for recorded birthweight?. Eur J Epidemiol. 2000, 16: 793-796. 10.1023/A:1007625030509.View ArticleGoogle Scholar
  51. O'Sullivan JJ, Pearce MS, Parker L: Parental recall of birth weight: how accurate is it?. Arch Dis Child. 2000, 82: 202-203. 10.1136/adc.82.3.202.View ArticleGoogle Scholar
  52. Andric SA, Kostic TS, Dragisic SM, Andric NL, Stojilkovic SS, Kovacevic RZ: Acute effects of polychlorinated biphenyl-containing and -free transformer fluids on rat testicular steroidogenesis. Environ Health Perspect. 2000, 108: 955-959.View ArticleGoogle Scholar
  53. Armstrong B, White E, Saracci R: Principles of Exposure Measurement in Epidemiology. Monographs in Epidemiology and Biostatistics. Edited by: Kelsey JL, Marmot MG, Stolley PD and Vessey MP. 1992, Oxford, New York, Tokyo, Oxford University Press, 21:Google Scholar
  54. Connor K, Ramamoorthy K, Moore M, Mustain M, Chen I, Safe S, Zacharewski T, Gillesby B, Joyeux A, Balaguer P: Hydroxylated polychlorinated biphenyls (PCBs) as estrogens and antiestrogens: structure-activity relationships. Toxicol Appl Pharmacol. 1997, 145: 111-123. 10.1006/taap.1997.8169.View ArticleGoogle Scholar
  55. Kodavanti PR, Kannan N, Yamashita N, Derr_Yellin EC, Ward TR, Burgin DE, Tilson HA, Birnbaum LS: Differential effects of two lots of aroclor 1254: congener-specific analysis and neurochemical end points. Environ Health Perspect. 2001, 109: 1153-1161.View ArticleGoogle Scholar
  56. Longnecker MP, Wolff MS, Gladen BC, Brock JW, Grandjean P, Jacobson JL, Korrick SA, Rogan WJ, Weisglas-Kuperus N, Hertz-Picciotto I, Ayotte P, Stewart P, Winneke G, Charles MJ, Jacobson SW, Dewailly E, Boersma ER, Altshul LM, Heinzow B, Pagano JJ, Jensen AA: Comparison of polychlorinated biphenyl levels across studies of human neurodevelopment. Environ Health Perspect. 2003, 111: 65-70.View ArticleGoogle Scholar
  57. al-Saleh I, Shinwari N, Basile P, el-Doush I, al-Zahrani M, al-Shanshoury M, el-Din Mohammed G: DDT and its metabolites in breast milk from two regions in Saudi Arabia. J Occup Environ Med. 2003, 45: 410-427. 10.1097/01.jom.0000058344.05741.22.View ArticleGoogle Scholar
  58. Pre-publication history

    1. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/content/backmatter/1476-069X-3-1-b1.pdf

Copyright

© Karmaus and Zhu; licensee BioMed Central Ltd. 2004

This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

Advertisement