Table 3 Representing characteristics of articles chosen for inclusion for current study

PON1 and neurodevelopment in children from the CHAMACOS study exposed to organophosphate pesticides in utero.

Eskenazi et al. [5]

n = 353 (children of participants of the CHAMACOS study)

Longitudinal birth cohort

Dialkyphosphate and metabolites. GCMS

PON1 (-108T)

PON1 (192 QQ)

Mental Development Index (MDI)

Bayley Scale of Infant Development (BSID)

Psychomotor Development Index (PDI)

Age 2 year olds

PON1 (-108) = − 3.2 (− 9.8–3.5), p = 0.98 (MDI) = − 2.3 (− 7.8–3.3), p = 0.91 (PDI)

PON1 (-192) = − 6.5 (− 15.6–2.6), p = 0.33 (MDI) = − 1.7 (− 8.7–5.4), p = 0.53 (PDI)

PON1_−108T related to MDI and, to a lesser extent, PDI in toddlers. Adds to the growing evidence that the PON1 gene is associated with an array of neurologic end points in adults and in children

Organophosphate pesticide exposure, PON1 and neurodevelopment in school-age children from the CHAMACOS study

Eskenazi et al. [21]

[K-CPT] (n = 296)

{WISC-IV]-(n = 327)

Longitudinal birth cohort

DAP and metabolites. GCMS

Enzymatic activity of ARYse and POase. Spectrophotometer

PON1 (-108T)

PON1 (-192Q)

Conners’ Kiddie Continuous Performance Test (K-CPT) at 5 years old and the Wechsler Intelligence Scale for Children (WISC-IV) at 7 years old

WISC positively associated with ARYase, 95% CI = 1.6, 6.4

PON1₋₁₀₈ weakly modified DAPS and K-CPT scores (p = 0.21) and WISC verbal IQ (p = 0.71)

DAPs and IQ strongest for children of mothers with lowest-tertile ARYase levels (p = 0.27)

PON1 enzyme levels during pregnancy may also increase susceptibility of children to neurotoxicity from OP pesticide exposure

Urinary organophosphate insecticide metabolite concentrations during pregnancy and children’s interpersonal, communication, repetitive and stereotypic behaviours at 8 years of age. The home study

Millenson et al. [26]

W = 224 mothers (PON1R192Q: n = 531, PON1L55M: n = 458) and children (PON1R192Q: n = 532, PON1L55M: n = 478)

Birth cohort

OP and metabolites.

Samples analysed by CDC

PON1 (R192Q)

PON1 (L55M)

Conners’ Parent Rating Scales-Revised (CRS-R), Conners’ Continuous Performance Test (CPT)

Behaviour Assessment System for Children-2 (BASC2)

Age 8 years

PON1−108TT genotype, ΣDAP concentrations were associated with 2.5-point higher (95% CI − 4.9, 9.8) SRS scores; however, the association was not different from the 1.8-point decrease (95% CI − 5.8, 2.2) among children with PON1−108CT/CC genotypes (ΣDAP × PON1−108 p value = 0.54). The association between ΣDAP concentrations and SRS scores was not modified by PON1192, p = 0.89

Maternal PON1192QQ associated with PON155MM and parent reported ADHD-LP in children

Maternal genotype significantly associated with ADHD-LP

Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene–environment interactions

D’Amelio et al. [27]

177 Italian and 107 Caucasian-American

Case control study

OP diazinone. HPLC

PON1 C 108T, L55M and Q192R

ASD-diagnosis, method not specified

Age: population based/not specified

(Q192R: v2 ¼ 6.33, 1 df, p = 0.025), transmission/disequilibrium tests (Q192R: TDT = 5.26, 1 df, p = 0.025), family based association tests (Q192R and L55M: FBAT Z = 2.291 and 2.435 respectively, p = 0.025) and haplotype-based association tests (L55/R192: HBAT Z = 2.430, p = 0.025)

Caucasian-American and not Italian families display a significant association between autism and PON1 variants, OP exposure could be implicated in Autism

Paraoxinase 1 activities and polymorphisms in autism spectrum disorders

Pasca et al. [28]

n = 50 ASD and 30 control

Case control study

No pesticide mentioned

PON1 (Q192R) and PON1 (L55M)

Diagnostic and statistical manual of mental disorders, fourth edition revised (DSM-IVR)

Age 6–7 years old

PON1 arylesterase and PON1 paraoxonase activities were decreased in autistic patients (respectively, p < 0.001, p < 0.05), no association between genotype and autism distribution

Bioavailability and the catalytic activity of PON1 are impaired in ASD

Prenatal exposure to organophosphates, paraoxonase 1 and cognitive development in childhood

Engel et al. [29]

Mothers (n = 360)

Children 1 year (n = 200), 2 years (n = 276) and 6–9 (n = 169) years of age

Prospective Multiethnic cohort

Organophosphate and metabolites. GCMS

PON1 (Q192R)

The Bayley Scales of Infant Development, 2nd edition (BSID-II)

Age 12 moths, 24 months and 6–9 year olds

ΣDAP and ΣDMP tertials of exposure were associated with a decrease in the MDI [log10 ΣDAP, β = − 3.29; 95% confidence interval (CI), − 5.88 to − 0.70].

ΣDAP metabolite level was inversely associated with the 24-month MDI (β = − 2.08; 95% CI, − 4.60 to 0.44) in multivariate adjusted models

PON1 192 QR/RR genotype experienced approximately a 5-point decline on the MDI with each log10 unit increase in ΣDAP or ΣDMP

Exposure to organophosphates is negatively associated with cognitive development, particularly perceptual reasoning, with evidence of effects beginning at 12 months and continuing through early childhood