Motor development following in utero exposure to organochlorines: a follow-up study of children aged 5-9 years in Greenland, Ukraine and Poland

Abstract


Background

Prior studies on the association between prenatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) and child motor development have found contradicting results. Using data collected in the INUENDO cohort in Kharkiv (Ukraine), Warsaw (Poland) and Greenland (N = 1,103) between the years 2002 and 2012, we examined relations of prenatal exposure to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p′-DDE) and 2,2′,4,4′,5,5′-hexachlorobiphenyl (CB-153) on motor development and developmental milestones; crawling, standing-up and walking.

Methods

CB-153 and p,p′-DDE were measured in maternal blood in second or third trimester of pregnancy. Motor development was measured in terms of the parentally assessed screening tool Developmental Coordination Disorder Questionnaire 2007 and developmental milestones were assessed via retrospective parental reports of child age at the first time of crawling, standing-up and walking.

Results

We saw no associations between tertiles of CB-153 and p,p′-DDE or log-transformed exposures and retrospective reports of the developmental milestones crawling, standing-up and walking in infancy or the motor skills measured as developmental coordination disorder at young school age.

Conclusions

In utero exposure to CB-153 and p,p′-DDE was not associated with parentally retrospectively assessed developmental milestones in infancy or parentally assessed motor skills at young school age. The use of a more sensitive outcome measure may be warranted if subtle effects should be identified.

Keywords:
Child motor development; Developmental milestones; Dichlorodiphenyldichloroethylene (DDE); Organochlorines; Polychlorinated biphenyls (PCBs); Prenatal exposure
Background


Polychlorinated biphenyls (PCBs) have been widely used in industrial production, e.g. in capacitors, sealants, plasticizers, fire retardants and hydraulic fluids, but they were banned in the late 1970s in the United States and the early 1980s in Europe because of their environmental persistence [1],[2]. Also, the insecticide dichlorodiphenyltrichloroethane (DDT) and its main metabolite dichlorodiphenyldichloroethylene (DDE) are highly persistent in the environment, and although the agricultural use of DDT has been severely restricted through the regional United Nations Economic Commission for Europe and the Stockholm Convention [3], it is still used as disease vector control in some developing countries [4]. PCBs and DDE are lipophilic compounds which bio-accumulate in adipose tissue and, thus, the main exposure is through food consumption and breast feeding [5],[6]. The compounds pass the placental barrier and the fetus is exposed to approximately the same concentration of DDE as the mother when calculated on lipid basis [7],[8]. The level of PCBs in the fetus, however, seems to be somewhat lower than that of the mother although correlated [9]. PCBs and DDE can be detected in serum and breast milk samples from almost all women around the globe, causing the fetus and subsequent breast-fed baby to be exposed to the compounds during infancy [9]-[12].

A major contamination of rice oil by heated PCBs and degradation products in Taiwan in 1979 gave insight into the negative impact of high prenatal exposure on e.g. neurodevelopment [13],[14]. Animal studies later found decreased muscular strength [15] after high prenatal exposure to tetrachlorobiphenyl and reduced motor activity [16] after prenatal exposure to PCBs. However, results from epidemiological cohort studies are inconsistent: Higher in utero exposure to PCBs (3000- > 4000 μg/L) was related to a significant decrease in motor abilities indicated by 7–8 points decrease of the Psychomotor Development Index scores (PDI) in Bayley Scales of Infant Development (BSID) (a screening tool measuring children’s motor and mental abilities) compared with low exposure (0–900 μg/L) at six, 12 and 24 months in a birth cohort from North Carolina [17],[18]. The Collaborative Perinatal Project from 12 hospitals in the United States found no association between background levels (0–16.50 μg/L) of prenatal PCBs exposure and motor development in terms of PDI in a sample of prenatally PCB exposed children of 8 months of age [19]. A two-point decrease in PDI scores for every 10-fold increase of DDE has been observed at six months of age, but not at 12 and 24 months [20], and further, no association was found between prenatal DDE and motor development according to McCarthy Scales of Children’s Abilities (MSCA) in two Spanish birth cohorts [21]. In addition, no association was found between in utero DDE exposure and motor development using BSID or MSCA among infants of one month, toddlers of 30 months or children of 3.5-5 years [22]-[24]. However, in utero exposure to DDE has been associated with hyporeflexia at one month in a cohort of North American children [25] and 4 points lower PDI for each doubling of DDE [26]. Further, no inverse associations between prenatal DDE and motor skills were observed in later follow-ups of the large North Carolina cohort [17],[18].

In this cohort, we follow three populations of 1,103 children from Arctic and Europe with a large exposure span, which enables us to examine the relation between different levels of organochlorine exposures and child motor development in various parts of the world. Thus, the aim of this follow-up study was to examine the relations between prenatal exposure to p,p′-DDE and CB-153 and developmental milestones in infancy measured retrospectively and motor development assessed by the questionnaire “Developmental Coordination Disorder Questionnaire” in five to nine year old children in Greenland, Ukraine and Poland.