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Placental pathology predicts infantile neurodevelopment.

ABSTRACT: The aim of present study was to investigate the association of placental pathological findings with infantile neurodevelopment during the early 40 months of life. 258 singleton infants were enrolled in the Hamamatsu Birth Cohort for Mothers and Children (HBC Study) whose placentas were saved in our pathological division. To assess the infantile neurodevelopment, we used Mullen Scales of Early Learning (gross motor, visual reception, fine motor, receptive language, expressive language) at 10, 14, 18, 24, 32, and 40 months. For obtaining placental blocks, we carried out random sampling and assessed eleven pathological findings using mixed modeling identified 'Accelerated villous maturation', 'Maternal vascular malperfusion', and 'Delayed villous maturation' as significant predictors of the relatively lower MSEL composite scores in the neurodevelopmental milestones by Mullen Scales of Early Learning. On the other hand, 'Avascular villi', 'Thrombosis or Intramural fibrin deposition', 'Fetal vascular malperfusion', and 'Fetal inflammatory response' were significant predictors of the relatively higher MSEL composite scores in the neurodevelopmental milestones by Mullen Scales of Early Learning. In conclusion, the present study is the first to report that some placental pathological findings are bidirectionally associated with the progression of infantile neurodevelopment during 10-40 months of age.

SUBMITTER: Ueda M

PROVIDER: S-EPMC8850429 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Placental pathology predicts infantile neurodevelopment.

Ueda Megumi M Tsuchiya Kenji J KJ Yaguchi Chizuko C Furuta-Isomura Naomi N Horikoshi Yoshimasa Y Matsumoto Masako M Suzuki Misako M Oda Tomoaki T Kawai Kenta K Itoh Toshiya T Matsuya Madoka M Narumi Megumi M Kohmura-Kobayashi Yukiko Y Tamura Naoaki N Uchida Toshiyuki T Itoh Hiroaki H

Scientific reports 20220216 1

The aim of present study was to investigate the association of placental pathological findings with infantile neurodevelopment during the early 40 months of life. 258 singleton infants were enrolled in the Hamamatsu Birth Cohort for Mothers and Children (HBC Study) whose placentas were saved in our pathological division. To assess the infantile neurodevelopment, we used Mullen Scales of Early Learning (gross motor, visual reception, fine motor, receptive language, expressive language) at 10, 14, ...[more]

PMID: 35173199

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Project description:ObjectiveTo evaluate the relationship between maternal vascular malperfusion and acute intrauterine infection/inflammation with neonatal outcomes.MethodsThis was a retrospective study of women with singleton pregnancies who completed placenta pathological examination. The aim was to study the distribution of acute intrauterine infection/inflammation and maternal placental vascular malperfusion among groups with preterm birth and/or rupture of membranes. The relationship between two subtypes of placental pathology and neonatal gestational age, birth weight Z-score, neonatal respiratory distress syndrome, and intraventricular hemorrhage was further explored.Results990 pregnant women were divided into four groups, including 651 term, 339 preterm, 113 women with premature rupture of membranes, and 79 with preterm premature rupture of membranes. The incidence of respiratory distress syndrome and intraventricular hemorrhage in four groups were (0.7%, 0.0%, 31.9%, 31.6%, P < 0.001) and (0.9%, 0.9%, 20.0%, 17.7%, P < 0.001), respectively. The incidence of maternal vascular malperfusion and acute intrauterine infection/inflammation were (82.0%, 77.0%, 75.8%, 72.1%, P = 0.06) and (21.9%, 26.5%, 23.1%, 44.3%, P = 0.010), respectively. Acute intrauterine infection/inflammation was associated with shorter gestational age (adjusted difference -4.7 weeks, P < 0.001) and decreased weight (adjusted Z score -2.6, P < 0.001) than those with no lesions in preterm birth. When two subtype placenta lesions co-occurrence, shorter gestational age (adjusted difference -3.0 weeks, P < 0.001) and decreased weight (adjusted Z score -1.8, P < 0.001) were observed in preterm. Consistent findings were observed in preterm births with or without premature rupture of membranes. In addition, acute infection/inflammation and maternal placenta malperfusion alone or in combination were associated with an increased risk of neonatal respiratory distress syndrome (adjusted odds ratio (aOR) 0.8, 1.5, 1.8), but the difference was not statistically significant.ConclusionMaternal vascular malperfusion and acute intrauterine infection/inflammation alone or co-occurrence are associated with adverse neonatal outcomes, which may provide new ideas for clinical diagnosis and treatment.

Project description:ObjectiveAntenatal Doppler measurements of the fetal umbilical and cerebral circulations can predict perinatal complications; however, it is unclear if subtle variations in antenatal Doppler measurements are associated with long-term neurodevelopmental outcome. In this study, we examined whether antenatal Doppler measurements of the fetal-placental circulation are associated with cognitive and motor abilities and brain morphology in childhood.MethodsTo evaluate differences in long-term sequelae across the continuum of the umbilical and cerebral artery circulations in the general population, we utilized a population-based longitudinal cohort study approach. In women from the Generation R study, we measured second- and third-trimester umbilical artery pulsatility index (UA-PI). Children underwent non-verbal intelligence testing at 4-8 years of age, and at 8-12 years they underwent finger-tapping tests to measure fine motor skills, balance beam tests to measure gross motor skills and brain magnetic resonance imaging. We assessed the relationships between prenatal UA-PI and neurodevelopmental outcome using linear regression. We adjusted for child age and sex, maternal age, education, parity and smoking status.ResultsThe study sample included 2803 pregnancies. Higher third-trimester UA-PI was associated with poorer fine motor performance (0.41 (95% CI, 0.11-0.70) fewer taps on the finger-tapping test per 1 SD higher UA-PI) and gross motor performance (0.64 (95% CI, 0.20-1.08) fewer steps on the balance beam test per 1 SD higher UA-PI). One SD higher third-trimester UA-PI was also associated with 0.65 (95% CI, 0.04-1.25) points lower intelligence quotient; however, unlike the associations with motor abilities, this finding did not persist after correction for multiple testing. Higher second-trimester UA-PI was associated with smaller brain volume (6.1 (95% CI, 1.0-11.3) cm3 reduction per 1 SD higher UA-PI), but the association did not persist after correction for multiple testing.ConclusionHigher placental vascular resistance may have mild adverse effects on neurodevelopmental outcome at school age. While these effects are subtle at population level, we encourage future research into the role of early circulation in brain development. This information could be used to develop targeted interventions. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Project description:BackgroundNeurodevelopmental impairment is common in children with congenital heart disease (CHD), but postnatal variables explain only 30% of the variance in outcomes. To explore whether the antecedents for neurodevelopmental disabilities might begin in utero, we analyzed whether fetal brain volume predicted subsequent neurodevelopmental outcome in children with CHD.MethodsFetuses with isolated CHD and sociodemographically comparable healthy control fetuses underwent fetal brain magnetic resonance imaging and 2-year neurodevelopmental evaluation with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) and the Adaptive Behavior Assessment System, Third Edition (ABAS-3). Hierarchical regression evaluated potential predictors of Bayley-III and ABAS-3 outcomes in the CHD group, including fetal total brain volume adjusted for gestational age and sex, sociodemographic characteristics, birth measures, and medical history.ResultsThe CHD group (n=52) had lower Bayley-III cognitive, language, and motor scores than the control group (n=26), but fetal brain volumes were similar. Within the CHD group, larger fetal total brain volume correlated with higher Bayley-III cognitive, language, and motor scores and ABAS-3 adaptive functioning scores (r=0.32-0.47; all P<0.05), but this was not noted in the control group. Fetal brain volume predicted 10% to 21% of the variance in neurodevelopmental outcome measures in univariate analyses. Multivariable models that also included social class and postnatal factors explained 18% to 45% of the variance in outcome, depending on developmental domain. Moreover, in final multivariable models, fetal brain volume was the most consistent predictor of neurodevelopmental outcome across domains.ConclusionsSmall fetal brain volume is a strong independent predictor of 2-year neurodevelopmental outcomes and may be an important imaging biomarker of future neurodevelopmental risk in CHD. Future studies are needed to support this hypothesis. Our findings support inclusion of fetal brain volume in risk stratification models and as a possible outcome in fetal neuroprotective intervention studies.

Project description:BackgroundGestational exposure to polychlorinated biphenyls (PCBs) has been associated with elevated risk for neurodevelopmental disorders. Placental epigenetics may serve as a potential mechanism of risk or marker of altered placental function. Prior studies have associated differential placental DNA methylation with maternal PCB exposure or with increased risk of autism spectrum disorder (ASD). However, sequencing-based placental methylomes have not previously been tested for simultaneous associations with maternal PCB levels and child neurodevelopmental outcomes.ObjectivesWe aimed to identify placental DNA methylation patterns associated with maternal PCB levels and child neurodevelopmental outcomes in the high-risk ASD MARBLES cohort.MethodsWe measured 209 PCB congeners in 104 maternal serum samples collected at delivery. We identified networks of DNA methylation from 147 placenta samples using the Comethyl R package, which performs weighted gene correlation network analysis for whole genome bisulfite sequencing data. We tested placental DNA methylation modules for association with maternal serum PCB levels, child neurodevelopment, and other participant traits.ResultsPCBs 153 + 168, 170, 180 + 193, and 187 were detected in over 50% of maternal serum samples and were highly correlated with one another. Consistent with previous findings, maternal age was the strongest predictor of serum PCB levels, alongside year of sample collection, pre-pregnancy BMI, and polyunsaturated fatty acid levels. Twenty seven modules of placental DNA methylation were identified, including five which significantly correlated with one or more PCBs, and four which correlated with child neurodevelopment. Two modules associated with maternal PCB levels as well as child neurodevelopment, and mapped to CSMD1 and AUTS2, genes previously implicated in ASD and identified as differentially methylated regions in mouse brain and placenta following gestational PCB exposure.ConclusionsPlacental DNA co-methylation modules were associated with maternal PCBs and child neurodevelopment. Methylation of CSMD1 and AUTS2 could be markers of altered placental function and/or ASD risk following maternal PCB exposure.

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Placental pathology predicts infantile neurodevelopment.

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Placental pathology predicts infantile neurodevelopment.

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