Table 1 Characterstics of included studies with outcomes

Brown et al. 2014

(Finland)

−677 mothers of ASD were matched with 677 control.

-Covariates included maternal age, paternal age, number of previous births, maternal socioeconomic status, pre-term birth, low birthweight, maternal/ parental history of psychiatric disorders, and gestational week of the blood draw

80% increase in risk of ASD with elevated mCRP, in the highest decile (> 9.55 mg/dl), compared to the lowest decile (0.10–0.57 mg/dl) (OR = 1.80, 95% CI = 1.09–2.97, p = .02)

greater association for females, but no interaction between mCRP and gender or mental retardation.

significant association between increasing maternal CRP (as continuous variable) and risk of ASD (OR = 1.12, 95% CI = 1.02–1.24, p = 0.02

-Retrospective Case control study provides only weak evidence for association.

− 455 cases were excluded from sample of 1132).

-Many important confounding factors were not recorded

i.e. history of infection, or inflammatory disorder, genetic analysis, immunoglobulin levels, psychopathology in pregnancy, or ethnicity.

Koks et al. 2016

(Netherlands)

-mCRP levels in early pregnancy and Social Responsiveness Scale (SRS) scores in children at the age of 6 years were analyzed for 4165 mother-child pairs.

mCRP levels and SRS scores were found to be associated but sequential modelling with confounding factors made the association disappear.

no association between elevated levels of mCRP during early pregnancy and parent-reported autistic traits in children at the age of 6 years.

-Retrospective Case and control study provide

Weak evidence.

− 1042 mother-child pairs data excluded have younger mothers with different lifestyle i.e. more smoking.

Zerbo 2016

(USA)

-population-based nested case–control study with 500 children with ASD, 235 with developmental delay (DD) and 580 general population (GP)

− 2 phase study.

-First sample set. Median mCRP levels were lower in the mothers of children with ASD (1.28 mg/dl, interquartile range = 0.54–3.06)

compared with the mothers of GP controls (2.43 mg/dl, interquartile range = 0.61–3.82

-Median CRP levels were significantly lower in the mothers of children with ASD (1.94 mg/dl, interquartile range = 1.04–3.90) compared with the mothers of GP controls (2.40 mg/dl, interquartile range = 1.32–4.48

mCRP levels in mid-pregnancy were lower in mothers of ASD compared with controls. The maternal CRP levels in the upper third and fourth quartiles were associated with a 45 and 44% decreased risk of ASD, respectively (negative association)

-Retrospective case control study.

-Study has 2 phases with different sample size and different technique for mCRP measurement.