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ARTICLES:
Brenda Eskenazi, Amy R. Marks, Asa Bradman, Laura Fenster, Caroline Johnson, Dana B. Barr, and Nicholas P. Jewell
In Utero Exposure to Dichlorodiphenyltrichloroethane (DDT) and Dichlorodiphenyldichloroethylene (DDE) and Neurodevelopment Among Young Mexican American Children
Pediatrics 2006; 118: 233-241
[Abstract][Full text][PDF]
Sir – The paper by Eskenazi and colleagues has raised concerns about
the effect of in utero exposure to DDT and DDE on neurodevelopment in
Mexican American children. The findings are of interest to
environmentalists, policy-makers, child-health specialists and public-
health specialists. However, the paper’s conclusion that the study has
‘important implications for countries that are reconsidering or continuing
the use of DDT for malaria control..’, assumes that the results of this
study are conclusive, and should thus affect policy. I would like to raise
the following concerns about the study to illustrate that more data are
needed: (i) to provide conclusive evidence that in utero exposure to DDT
and (to a lesser extent DDE) may be associated negatively with
neurodevelopment and (ii) before policy-changes regarding DDT-use in
resource-limited countries where controlled spraying of DDT best
eradicates the malaria vector, can be recommended.
Sample: Although the data were gathered from participants in a
longitudinal birth cohort study our sense is that the 6, 12 and 24 months
data on development should be interpreted as assessments, at three time
points, on groups that slightly differed in their characteristics i.e. the
assessments do not represent developmental trajectories of the children
assessed at 6 months. This assumption is supported by the fact that data
are presented for 360 mothers (not 330). It would be important to see the
relationship between DDT and neurodevelopment in exactly the same group
of children at 6, 12 and 24 months. If the sample of children at 6, 12 and
24 months differ, one wonders whether the reasons for either missed visits
or missed assessments at 12 and 24 months were in any way related to
exposure or outcome.
Loss to follow-up/non-inclusion in analysis: Although the original
cohort was 601 women, blood levels of DDT were obtained for only 526
women, and the association between DDT/DDE levels and BSID scores were
only ascertained in 330, 327 and 309 children (6, 12 and 24 months
respectively) i.e. in a little more than half the original sample. It is
not clear how / whether the children / mothers excluded from the final
analysis differed from children/mothers included in the analysis. Were the
children included in the analysis at higher risk of obtaining lower
scores, for reasons other than DDT exposure? Did mothers who were excluded
have lower DDT/DDE levels, or would their infants have had poorer
neurodevelopmental outcomes than those included in the sample due to
reasons other than DDT?
Measuring exposure: Exposure was agricultural – It is not clear what
levels of agricultural exposure had led to the high blood DDT/DDE levels,
and whether controlled indoor household residual spraying of DDT for
malaria control (using a low dose - approximately 1-2g/m2) would produce
the same exposure level. Furthermore, mother’s blood level was used as a
proxy for infants exposure. Though this may be correct [1] , postnatal
exposure to DDT/DDE was not known, and thus not accounted for.
Measuring and interpreting outcome: The Bayley scales of infant
development (BSID) were used to measure mental and psychomotor
development, using the US population as a standard. Several issues are of
concern here: (i) The BSID may be used to describe the current
developmental functioning of infants However, their stability (repeated
measures using the same test) and predictive power are not high [2]. The
article, by stating that the study has implications for malaria control,
suggests that the decrease in BSID scores are clinically significant.
However, the original version of the BSID scale for infants and toddlers
up to 24 mo of age has failed to show construct and predictive validity.
Although BSIDII incorporated a new standardization of the mental scale it
has shed no new light on its construct validity up to the ages of 18–24
months [2,3,4]. Studies have shown that the median correlation between the
mental development scores obtained at some point between 7 and 12 months
and an IQ obtained sometime between 5 to 7 years of age was about 0.20
[5,6].This means that the finding that a 10-fold increase in p,p’-DDT,
o,p’-DDT, and p,p’-DDE levels were significantly associated with decreases
in 12- and 24-month MDI scores are likely to not have any bearing /
significance for later development and IQ.
Furthermore, although the analysis controlled for psychometricians, it
would have been useful to have conducted and reported on a preliminary
pilot to determine the correlation coefficients for intra and inter-
observer BSID scores.
Measuring confounders and other variables:
Postnatal exposure to other neurotoxicants, and other confounders such as
nutritional status (infants weight for age / weight for height at each
assessment), diet, type of delivery, length of second stage of labour,
birth trauma were not measured and controlled for. Did women with higher
DDT exposure also have other such characteristics that increased their
infant’s risk of getting low scores on the BSID?.
Furthermore although the study measured depressive symptomotology using a
standardized scale it is not clear how relevant and reliable this scale
was to identify depression in this newly immigrant population, and how
this may have affected the relationship between exposure and outcome.
Statistical analysis:
The statistical analysis treated DDT/DDE levels as a continuous variable –
possibly because the researchers believe that any exposure to DDT leads to
adverse outcome. It would be interesting to also see the analysis
conducted using DDT/DDE levels as a dichotomous variable (equal to or
above the geometric mean and below the geometric mean) to determine
whether the scores are significantly different. Furthermore, the analysis
in this study lumped all DDT exposures and outcomes, including the group
with no known exposure into one group. Future research on DDT exposure and
developmental outcome should, for public health purposes, look at exposure
and outcome for three different groups of mother-infant pairs: (i) known
agricultural exposure (ii) known exposure only through controlled indoor
household residual spraying (iii) no known exposure to DDT to determine
whether outcome differs significantly between groups.
Other issues of concern:
The authors report on standardized scores, which, in this population, are
lower than the expected mean standardized score for the US population. The
authors also do not state whether the BSID were modified to make them more
relevant to the newly immigrant population. It is not clear what each
mother was told about her child’s neurodevelopment, and future, in
relation to the scores obtained. Caution is usually warranted in using the
BSID for populations that differ from the standardization sample and some
examiners who use the BSID for research purposes report raw scores, rather
than relying on U.S. norms [7]
Furthermore, the assumption after reading the article is that BSID II was
used. BSIDII requires that examiners have training and experience in
administering and interpreting standardized assessments with infants as
test administration and interpretation is more complex than with other
standardized assessments because the examiner alters the sequence of items
in response to the infant’s behavior and performance [7]. Typically
examiners have training at the master’s or doctoral level and supervised
experience, in accordance with guidelines from the American Psychological
Association. The paper does not state the level of skill of the
pschometricians.
Looking forward:
As stated by the authors I agree that (i) the beneficial role of
breastfeeding, in the context of DDT use should be explored further,
particularly as breastfeeding is usually a norm in areas of high malaria
endemnicity, and in areas where DDT is currently being used for malaria
control (ii) the cohort assessed should be followed up and developmental
trajectories developed for each child to ascertain the clinical
significance of the results.
References
1. Waliszewski SM, Aguirre AA, Silva CS, Siliceo J. Organochlorine
Pesticide Levels in Maternal Adipose Tissue, Maternal Blood Serum,
Umbilical Blood Serum, and Milk from Inhabitants of Veracruz, Mexico.
Arch. Environ. Contam. Toxico. 2001; 40: 32–438.
2. Pollitt E. Statistical and psychobiological significance in
developmental research. American Journal of Clinical Nutrition. September
2001; 74:3, 281-282, .
3. McCall RB, Mash CW. Long-chain polyunsaturated fatty acids and the
measurement and prediction of intelligence (IQ). In: Dobbing J, ed.
Developing brain and behavior. San Diego: Academic Press, 1997:295–329.
4. Pollitt E, Triana N. Stability, predictive validity, and
sensitivity of mental and motor development scales and pre-school
cognitive tests among low-income children in developing countries. Food
Nutr Bull. 1999;20:45–52.
5. McCall RB. A conceptual approach to early mental development. In:
Lewis M, ed. Origins of intelligence. 2nd ed. New York: Plenum Press,
1983:255-301.
6. McCall RB. The development of intellectual functioning in infancy
and the prediction of later IQ. In: Osofsky JD, ed. Handbook of infant
development. New York: Wiley, 1979:704-41.
7. Black MM, Matula K. Essentials of Bayley scales of infant
development. II. Assessment. New York, NY: Wiley, 2000.
*Ameena Goga is supported by CAPRISA which forms part of the
Comprehensive International Program of Research on AIDS (CIPRA) funded by
the National Institute of Allergy and infectious Disease (NIAID), National
Institutes of Health (NIH) and the US Department of Health and Human
Services (DHHS) (grant# 1 U19 AI51794), and the Columbia University-
Southern African Fogarty AIDS International Training and Research
Programme (AITRP) funded by the Fogarty International Center, National
Institutes of Health (grant # D43TW00231.
Conflict of Interest:
None declared
Dichlorodiphenyltrichloroethane. Implications of Eskenazi et al study to malaria control in Africa
15 August 2006
BARNABAS N KAHIIRA, Public Health Braun School of Public Health
Reference is made to the article on the effects of DDT and it
degraded form DDE on neurodevelopment of young Mexican American children
by Eskenazi et al1 that recently appeared in Pediatrics. I would like to
commend the authors for undertaking this study; the first of its kind to
prospectively assess the direct effects of DDT on human subjects. That
said, I have several methodological and statistical considerations to
highlight that I think may limit our interpretation of their findings.
To begin with, though the researchers measured several prenatal and
post natal exposures, I am worried why they did not prospectively measure
the nutritional status of these infants and children particularly their
hemoglobin status. Studies have demonstrated that anemic infants and young
children are more likely to be mentally retarded than those who are non
anemic2 and that micronutrient supplements containing iron can improve
children's mental development.3 The authors of this study, without
assessing variables associated with iron deficiency and supplementation of
these young Mexican children leave us to suspect that the observed
relationship though minor may be explained easily by a third variable.
Secondly, it must be noted that although they measured and included
maternal depressive symptoms in the analytical models, only the models
where this important variable is not included in the analysis show
significant results. Indeed about 52% of the participating women screened
positive for depression in their study. Motor and early development of
children is known to depend on their mother's mental health status such as
depression,4-5 one would have expected the researchers to keep this
variable whether significant or not in the final models so as to make
meaningful inferences. The authors do not tell us why maternal depression
is presented in models with no significant results but not in the models
showing significant results.
Thirdly, Eskenazi et al performed several statistical comparisons in
their study. However, they did not adjust for this in their statistical
methods. Surely they present several p-values and it turns out that only
two are significant at á=5%. The third p-value they indicate to be
significant is only so at p<0.10! The effect of multiple comparisons on
study results and how these can be remedied has been described by others.6
-7 We can't rule out the risk that these p-values might be significant
just by chance alone.
Last but not least, even if we were to take their findings as being
right, we need to ask their relevance to the use of DDT in malaria control
now being advocated for around the world. This is particularly important
in Africa; as the World Health Organisation (WHO) estimates that 90% of
around one million malaria deaths worldwide take place in the impoverished
continent.8 Mexico where the study participants migrated from; DDT use
was, until its recent ban, carried out largely outdoors permitting
widespread environmental contamination and bioaccumulation in animal
tissues. This very much contrasts the controlled use of DDT through indoor
residual spray (IRS) being sought today. With controlled use of DDT
through IRS, it's entry into the food chain and ecosystem can be kept at
very minimal levels. Again studies have shown that DDT easily degrades
under relatively higher temperatures, as exists in tropical Africa, to its
breakdown product DDE.9 With their study showing no association between
maternal DDE levels with children's neurodevelopment, I would think that
this further dilutes the relevance of the effects of DDT observed in this
study even if we were to take the findings seriously.
With all these inconclusive results and graphical presentations
showing ideally no trend, I would like to ask the authors what their
recommendation would be, to a country in Sub-Saharan Africa such as Uganda
which estimates to lose at least 320 lives to malaria daily (Ugandan
press) bearing in mind the ever-growing resistance to antimalarial drugs
and lack of cost-effective alternatives to DDT.
Thank you
Barnabas Natamba Kahiira
Braun School of Public Health and Community Medicine
Hebrew University of Jerusalem
REFERENCES
1. Eskenazi B, Marks AR, Bradman A, et al. In Utero Exposure to
Dichlorodiphenyltrichloroethane and Dichlorodiphenyldichloroethylene and
Neurodevelopment Among Young Mexican American Children Pediatrics 2006;
118; 233-241
2. Krieger HE, Claussen AH, Scott KG Early childhood anemia and mild
or moderate mental retardation American Journal of Clinical Nutrition,
1999; 69:115-119.
3. Saco-Pollitt C, Pollitt E, Harahap H, Jahari AB, Husaini MA.
Effects of an energy and micronutrient supplement on iron deficiency
anemia, physical activity and motor and mental development in
undernourished children in Indonesia. European journal of Clinical
Nutrition 2000; 54: S114-S119
4. Gross D, Conrad B, Fogg L, Willis L, Garvey C. A longitudinal
study of maternal depression and preschool children's mental health. Nurs
Res. 1995; 44: 96-101.
5. Murray L, Fiori-Cowley A, Hooper R, Cooper P. The Impact of
Postnatal Depression and Associated Adversity on Early Mother-Infant
Interactions and Later Infant Outcome. Child Development1996; 67: 2512-
2526
6. Bland JM, Altman DG Multiple significance tests: the Bonferroni
method. BMJ 1995; 310:170
7. Voss S and George S Multiple significance tests BMJ 1995 310:
1073.
8. Samuel T, and Pillai MK The effect of temperature and solar
radiations on volatilisation, mineralisation and degradation of [14C]-DDT
in soil. Environ Pollut. 1989; 57: 63-77
9. WHO (World Health Organization). Malaria in Africa. Roll Back
Malaria Initiative. Available on
http://www.who.int/mediacentre/factsheets/fs094/en/ Accessed on July 14,
2006
Conflict of Interest:
None declared
Re: Dichlorodiphenyltrichloroethane. Implications of Eskenazi et al study to malaria control in Afri
24 August 2006
Brenda Eskenazi, Director, Center or Children's Environmental Health Research School of Public Health, UC Berkeley, Amy R. Marks, Asa Bradman, Caroline Johnson, Nicholas P. Jewell
We thank Dr. Kahiira for his commendations and comments. We try to
address each of his concerns below:
1. Concern that we did not control for nutritional status of
children, in particular hemoglobin status: Although a child’s hemoglobin
status may be related to neurodevelopment, there is no evidence in the
literature that iron deficiency is related to DDT exposure, and therefore
it is not likely to be a true confounder. Nevertheless, we re-ran our
models controlling for iron deficiency based on hematocrit values recorded
in the medical record near the time of the assessments. We found that iron
deficiency was not associated directly with DDT or Bayley scores and did
not change the observed associations with DDT/E.
2. Concern that we did not control for maternal depression in some
models: Based on the literature, we considered maternal depressive
symptoms as a possible confounder in all analyses. As described in the
paper, a variable was included in the multivariate models if it was
related to the outcome at p<0.10 or changed the coefficient for DDT or
DDE by at least 10%.[1] The only Bayley model in which there was even a
weak association with maternal depression was with psychomotor development
index (PDI) at 24 months. Thus, the variable for maternal depressive
symptoms was not included in the mental developmental index (MDI) models
because it did not fulfill these criteria.
3. Concern that we did not adjust for multiple comparisons: We first
note that Dr. Kahiira misread our findings in that we had 7 (not 2)
negative associations at p<0.05: o,p’-DDT with MDI at 12 and 24 months
(p<0.01); p,p’-DDT with MDI at 12 and 24 months (p<0.05); p,p’-DDT
with PDI at 6 and 12 months (p<0.05); and p,p’-DDE with PDI at 6 months
(p<0.05)(Table 3 of manuscript[1]).
While Dr. Kahiira raises an important issue with regard to adjustment
for multiple comparisons, this is not as serious a concern as it might
appear at first glance. Because of the interrelationships amongst the
exposures and amongst the outcomes, the 18 comparisons shown in Table 3[1]
are not independent. The serum levels of the three analytes (p,p-DDT, o,p,
-DDT, and p,p-DDE) were highly correlated (pairwise r=0.8 to 0.9;
p<0.001 [1]); we reported their findings separately because their high
degree of collinearity prevented us from modeling them simultaneously. In
addition, MDI and PDI were moderately correlated at each of the three time
points (r=0.3 to 0.6; p<0.001) and, although not as strong, across ages
(r=0.1 to 0.3; p<0.04). Thus, a Bonferroni correction might be
considered unduly conservative. [2] Nevertheless, even employing a
Bonferroni adjustment for six independent comparisons (allowing for
independence of outcomes but not of exposures), our findings for MDI and
o,p,-DDT at 12 (p=0.004) and 24 months (p=0.007) would still be considered
“statistically significant” at á=0.05.
Further, the evaluation of the relationship of DDT and
neurodevelopment should not focus solely on the issue of statistical
significance. While perhaps not clinically relevant on an individual
level, a few points on the Bayley MDI scale may be relevant at a
population level. That is, a downward shift in the distribution of a
population’s neurodevelopmental scores could result in a larger fraction
of children falling in the tail of the distribution with clinically
significant developmental problems.
4. Concern about the relevance of our findings to current use of DDT
for malaria control: A recent study of DDT levels in breastmilk in South
African women living in regions where DDT has been used for IRS[3] suggest
that exposures are at least as high as those in our study (adjusting for
the ratio of DDT in breastmilk and serum[4]), which were associated with
decrements in child neurodevelopment. However, it is not possible to
determine the specific sources and pathways of DDT exposure in these
populations, which may be due to environmental contamination from
agricultural use, residues in the food supply, broadcast applications for
public health purposes, or indoor uses on nets or interior residual
spraying (IRS) for malaria control. To date, surprisingly little
quantitative data have been published about the specific contribution of
IRS to human DDT exposure.
Dr. Kahiira reports that DDT readily breaks down to DDE in the high
temperatures of tropical countries, and therefore, he concludes, there is
less concern about DDT use given that our findings with DDE were weaker.
However, IRS is recommended every six to twelve months[5] and repeated DDT
spraying may lead to continuous exposure. Given its long half-life in
humans (~6 years[6]), DDT might accumulate in the human body with regular
use even if it breaks down to a less biologically active product in the
environment. Again, empirical data on the specific contribution of IRS to
human DDT exposures is needed.
The cost of malaria in terms of human suffering is undeniably high.
We are not in a position to endorse a particular policy regarding the use
of DDT as an efficacious method for controlling this horrific disease, but
rather we offer our research to help inform those who are making such
policy decisions. Clearly, our research, the first to study the
association between neurodevelopment and DDT, needs to be confirmed in
other populations, and the children in our study should be followed to
determine if our findings persist as the children enter the school years.
Exposure in human populations should be monitored and potential health
consequences should be studied to inform policy.
Thank you.
REFERENCES
1. Eskenazi B, Marks AR, Bradman A, et al. In utero exposure to
dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene
(DDE) and neurodevelopment among young Mexican American children.
Pediatrics 2006;118(1):233-41.
2. Bland JM, Altman DG. Multiple significance tests: the Bonferroni
method. Bmj 1995;310(6973):170.
3. Bouwman H, Sereda B, Meinhardt HM. Simultaneous presence of DDT
and pyrethroid residues in human breast milk from a malaria endemic area
in South Africa. Environ Pollut 2006.
4. Waliszewski SM, Aguirre AA, Infanzon RM, Siliceo J. Persistent
organochlorine pesticide levels in maternal blood serum, colostrum, and
mature milk. Bull Environ Contam Toxicol 2002;68(3):324-31.
5. World Health Organization. Frequently asked questions on DDT use
for vector control. Geneva: World Health Organization; 2005.
6. Wolff MS. Half-lives of organochlorines (OCs) in humans. Arch
Environ Contam Toxicol 1999;36(4):504.
Conflict of Interest:
None declared
Re: DDT and neurodevelopment: results inconclusive to effect policy change
22 September 2006
Brenda Eskenazi, Director, Center for Children's Environmental Health Research School of Public Health, University of California, Berkeley, Amy R. Marks, Asa Bradman, Caroline Johnson, and Nicholas P. Jewell
We thank Dr. Goga for her
thoughtful feedback. First, we agree that no single epidemiologic investigation
should be considered conclusive and that our study results clearly need to be
replicated in other populations, but we also believe that all data from
well-conducted studies, conclusive or not, should be considered for policy
decisions. We try to address each of her specific concerns below:
1. Sample: There were 281 children with DDT/E measurements
and Bayley assessments at all three ages. When
multivariate analyses were limited to these children and compared to those for
the full sample available at each time, the patterns of associations were
similar and, in most cases, the coefficients and p-values were stronger,
despite the smaller sample sizes. Also, we conducted longitudinal analyses, as
stated in the text [1], and the results were similar.
2. Loss to follow-up/non-inclusion in analysis: While 601
women were enrolled in the study [1], 20 miscarried, 5 neonates/fetuses died,
and 43 dropped (mostly due to relocation) before delivery, leaving 531 followed
past delivery and 476 followed to 6 months. We performed Bayley
assessments at least once on 459 children, or on 86% of infants alive and in
the study following delivery. Blood levels of organochlorines
were measured for 426 women (rather than 526 as stated by Dr. Goga), yielding an overlap with Bayley
assessments of 364 children; those not analyzed were due to lack of a stored
serum sample of adequate volume. As suggested, to investigate potential bias
introduced by non-inclusion, we made the following comparisons:
a. We compared the baseline
demographic characteristics of those in the original cohort and the sample
included in the paper (i.e., those who had both DDT/E levels and Bayley scores) and found that women not included were more
likely to smoke and were less likely to be married or living as married.
Controlling for these factors did not alter our results.
b. We compared exposure levels in
those who had a Bayley assessment performed at all
time points and those who did not and found no significant differences in DDT
or DDE levels.
c. We compared the Bayley scores of those who had DDT/E levels and those who
did not and found that Bayley scores did not differ
at 24-months where we observed the strongest associations. However, children
without DDT/E measurements had lower 12-month MDI.
We further note that selection bias arising from
non-inclusion solely on the basis of high or low Bayley
scores would tend to bias the association with DDT/E exposure towards the null.
Selection bias on the basis of exposure is irrelevant since all regression
analyses already condition on the observed values of the explanatory variables.
3. Measuring exposure: It is not possible to know the
proportion of the DDT/E levels observed in this population due to agricultural
exposure versus anti-malaria efforts. Women in our study who were born in
coastal Mexico had
significantly higher levels of DDT and DDE than those who did not, and levels
increased with the number of years spent outside of the U.S. [2].
In northern and central Mexico,
agricultural DDT use declined in mid-1970s in response to U.S. import standards for OC
residues [3], and in 1990 the Cicoplafest commission
seriously restricted DDT use, which was then banned nationwide in 1997 for
purposes other than public health use inside dwellings. DDT use for malaria
control continued in coastal areas until 2000.
To date, very little information has been published on
exposure resulting from IRS with DDT. Background levels in individuals living
in African nations with historical or current DDT use appear to be at least as
high [4,5] as those observed in our population (please
see our response to Kahiira). Thus, although we do
not know the precise source of the DDT in our population, if populations living
in areas with IRS spraying have maternal serum levels comparable to or higher
than those in our study, then the associations we observed would still be
relevant.
We do not currently have postnatal exposure information, but
we attempted to account for postnatal exposure by using as a proxy the duration
of breastfeeding, which is the primary source of postnatal exposure in children
in the U.S.
We also aimed to estimate postnatal exposure more precisely by examining the
interaction between maternal levels of DDT/E and the duration of breastfeeding.
4. Measuring and interpreting outcome: The Bayley Scales of Infant Development II is a well-known
assessment of infant development. We agree that any assessment of infants can
have limited predictive validity, and we do not know the predictive validity of
this test in this population. These issues necessitate both follow-up of these
children into school age and similar studies in other populations. In the
meantime, this study indicates a relationship within our population between
maternal serum levels of DDT and neurodevelopment by age two years. Unless
there was a systematic bias introduced in the assessment, i.e., all those with
high exposure were assessed in a different manner, these associations merit
consideration.
5. Measuring confounders and other variables: We considered
for analyses many of the covariates mentioned by Dr. Goga,
but did not consider any variables that were not considered in the literature
to be related to the exposure or outcome or were possibly on the causal
pathway.We considered pertinent medical
conditions, including those resulting from birth trauma, and the few children
affected were excluded from the study either de facto (i.e. they were not
assessed or valid scores could not be calculated) or in the data analysis. We
have not yet measured postnatal exposure to neurotoxicants
other than lead, which was low. To account for the associations observed,
postnatal exposure to other neurotoxicants would need
to be associated with prenatal DDT/E levels and unrelated to prenatal levels of
the same chemicals, which we did consider in analyses.
The CES-D is a well-regarded tool to screen for maternal
depression in epidemiologic investigations. Although available in Spanish, we
agree it may not be a valid tool in an immigrant population. Nevertheless, the
limitations of the instrument are consistent across this homogeneous
population. We are not sure how the limitations of the CES-D would alter the
conclusions of the present study on the associations of DDT and
neurodevelopment.
6. Statistical analysis: We followed Dr. Goga’s
suggestion to examine neurodevelopment by dichotomous exposure. Thus, we
compared children with prenatal DDT/E exposure in the highest quartile to children whose exposure fell in the lowest quartile,
controlling for the same covariates described in the paper (see Table 1 below).
These new results are entirely consistent with the findings presented in the
paper.
Specifically, as shown in Table 1, children in the highest
quartile of prenatal exposure to p,p’-DDT and p,p’-DDE had
significantly lower mean PDI scores at 6 and 12 months (-3.3 to -5.8 points)
and borderline lower mean PDI scores for p,p’-DDT at
24 months (-2.8 points) than children in the lowest quartile. Relative to the
least exposed children, children in the highest quartile of both p,p’-DDT and o,p’-DDT exposure
had significantly lower mean MDI scores at 12 months (-3.4 to -4.2 points), and
children most highly exposed to both isomers of DDT and to DDE, had
significantly lower mean MDI scores at 24 months (-4.0 to -5.1 points).
Regarding Dr. Goga’s other point
about the source of exposure, as stated above, the serum DDT/E measures
represent body burden. It is not possible to identify the source of the
exposure, nor does it call into question the observed association. Furthermore,
very little information is presently available on DDT exposure resulting from
IRS, and there is a need for further exposure monitoring and research.
Table 1. Mean differences (95% CI)
for points on the Bayley Psychomotor Development
Index (PDI) and Mental Development Index (MDI) for highest versus lowest
quartile of serum levels of p,p’-DDT, o,p’-DDT, and p,p’-DDE inCHAMACOS
cohort.
Models control for the same
covariates summarized in Table 3 of original paper.
Children in middle quartiles
of exposure were not included in these models.
*p<0.10
** p<0.05
*** p<0.01
7. Other issues of concern: As stated in the paper [1], mean
Bayley PDI scores at 6, 12, and 24 months were 96.4,106.7, and 97.8, respectively; mean MDI scores were95.4,
100.9, and 86.0.With the single exception of the 24-month MDI, these were all
close to the expected mean score of 100, which would seem to indicate that
using the age-standardized scores is not entirely unwarranted. If a child
performed more than two standard deviations below the norm, the child’s
guardian was informed, the child was referred to his or her pediatrician for
further assessment, and study staff spoke to the pediatrician. Such assessments
were excluded from these analyses since they were outliers.
The assessments were done for research, not clinical
purposes, and the parents and clinicians were informed of this. We considered
them inappropriate for clinical purposes, because we translated the instrument
to Spanish (yet made no other modifications to the instrument), and although
the psychometricians performing the assessments were
trained extensively and were clinically supervised, they did not have graduate
degrees. Given the paucity of bilingual psychologists in this community, we
believed it was paramount to have assessments completed by bilingual bicultural
members with experience with children from their community. Thus, these assessments
were purely for research purposes to enable comparison of neurodevelopment
within this population. While it is important to acknowledge the shortcomings
of this instrument and administration, the relevant issue here is whether the
methods of administration would alter the association of DDT and
neurodevelopment in this population. Assessors were blind to DDT levels and
exposure-related factors, thus there is no reason to believe that they would
have been systematically biased in their assessments based on children’s
exposures.
In summary, we agree that more data are needed on IRS
exposure, that the children in the present cohort should be followed to
determine the persistence of the observed associations and the contribution of
breastfeeding, and that other studies should be conducted to examine these
associations within other populations. In the meantime, we believe that it is
for policy makers to weigh the benefits and risks of DDT use using all the data
available.
Thank you.
REFERENCES
1. Eskenazi B, Marks AR, Bradman A, et al. In utero
exposure to dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene
(DDE) and neurodevelopment among young Mexican American children.
Pediatrics 2006;118(1):233-41.
2. Bradman A, Schwartz JM, Fenster L, Barr D, HollandNT, Eskenazi B. Factors predicting organochlorine
pesticide levels in pregnant women living in the Salinas Valley, California.
JESEE 2006;In Press.
3. U.S.
DHHS. Toxicological profile for DDT, DDE, and DDD.Atlanta, GA: U.S. Dept. of
Health and Human Services Public Health Service, Agency for Toxic Substances
and Disease Registry; 2002.
4. Bouwman H,
Sereda B, Meinhardt HM. Simultaneous presence of DDT
and pyrethroid residues in human breast milk from a
malaria endemic area in South
Africa. Environ Pollut
2006.
5. Waliszewski SM, Aguirre AA, Infanzon RM, Siliceo J.
Persistent organochlorine pesticide levels in maternal blood serum, colostrum, and mature milk. Bull Environ ContamToxicol 2002;68(3):324-31.
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