Association between Placental Inflammatory Pathology and Offspring Neurodevelopment at 8 Months and 4 and 7 Years of Age

A systematic review of the biological, social, and environmental determinants of intellectual disability in children and adolescents

“…Among the 58 studies ( 13 , 29 – 85 ) included in this systematic review, there were 20 population-based cohort studies ( 13 , 29 , 36 , 42 , 45 , 46 , 56 , 60 – 64 , 66 – 68 , 72 , 77 , 80 , 82 , 84 ), 20 other cohort studies ( 31 , 34 , 35 , 37 , 40 , 44 , 48 – 55 , 59 , 69 , 71 , 73 , 81 , 83 ), 14 case–control studies ( 32 , 33 , 39 , 41 , 47 , 57 , 58 , 65 , 70 , 75 , 76 , 78 , 79 , 85 ), and four studies with cross-sectional study designs ( 30 , 38 , 43 , 74 ) ( Table 1 ). These studies were published from 1984 to 2020 and were predominantly based in North America ( n = 33), Europe ( n = 13), and Australia ( n = 10).…”

“…However, no reason was found for downgrading the certainty of evidence. Two recent studies assessing mid-gestational cytokine and chemokine levels as markers of inflammation were not comparable and thus ineligible for GRADE analysis but provided fairly weak evidence of an increased risk of offspring ID despite some impact on developmental progress ( 65 , 81 ).…”

Are there sex differences in fetal growth strategies and in the long-term effects of pregnancy complications on cognitive functioning?

“…We do so using a large dataset that allows us to examine birthweights, placental weights as well as cognitive outcomes at 7 years of age in the same population, the National Collaborative Perinatal Project (NCCP).The NCCP collected data from ~60,000 pregnancies, including information about pregnancy outcome, placental pathology, and follow-up psychological exams at various ages, 26 and so provides the opportunity to test hypotheses regarding sex differences in fetal strategies and the long-term effects of early-life environment. Although the NCCP began over 60 years ago, the data are of good quality 26,27 and it forms the basis for many recent studies of placental pathology, [28][29][30][31] cognitive development, [32][33][34][35][36] and other epidemiological questions. [37][38][39][40][41][42] Importantly for the present study, the biology underlying sex differences in fetal growth strategies would not have changed over this time period, and most of the variables used (e.g., birthweight, placental weight, and gestational age at birth) are straightforward to measure.…”

Placental morphology in association with autism-related traits in the EARLI study

“…Although our study did not observe associations between placental morphological features and cognitive development as measured by the MSEL ELC, some studies have suggested links with related features and similar outcome measures. One prior study has demonstrated relationships between low-placenta-to-birthweight ratio and delayed neurodevelopment measured by the MSEL at seven time points, from 1 month to 24 months of age [ 19 ], while other studies reported links between placental inflammatory pathology (indicated by histologic chorioamnionitis) [ 20 ], placental abruption [ 22 ], placental chorionic plate diameters, disk thickness [ 21 ] and adverse child neurodevelopment according to Bayley motor and mental scales at 8 months and/or lower IQ scores at 4 and 7 years [ 20 – 22 ], Additionally, one study suggested positive associations between placental size (weight, surface area and placental-to-birth-weight ratio) and mental health problems in boys at 8 and 16 years of age indicated by the Rutter B2 scale [ 23 ]. An analysis of the CHARGE (Childhood Autism Risks from Genetics and the Environment) study also suggested that placental insufficiency plays a role in developmental delays, given an association between self-reported severe preeclampsia and scores on the MSEL and Vineland Adaptive Behavior Scales at ages 2 to 5 years [ 53 ].…”

“…Furthermore, placental morphological features and complications have been linked not only with birthweight [4,10,11], fetal growth restriction (FGR) [12] and preterm delivery [13], but also Apgar scores [14], motor development and cerebral palsy [15], and longer-term child outcomes including body mass index (BMI), cardiovascular disease, hypertension, and asthma [11,[16][17][18]. Placental morphological features and complications like placental inflammation and abruption have also been associated with delayed neurodevelopment as indicated by lower scores on cognitive assessments, as well as antisocial behavior, and attention deficit hyperactivity disorder [4,[19][20][21][22][23]]. Yet it is not clear how these features may relate to other specific neurodevelopmental conditions like autism spectrum disorder (ASD).…”