Prenatal exposure to maternal steroid hormones and child neurodevelopment: evidence for sex-specific effects in a longitudinal birth cohort
The 5 matches
- [1] § Cross-cohort consistency analysis ↔ scripts/7_EWAS_BiSC_hormones_neuro.R, lines 1–71 · score 0.96 · linear regression models, maternal ethnicity, missForest, maternal BMI, nursery attendance, passive smoking
- [2] § Discovery analysis in the INMA-Sabadell cohort ↔ scripts/6_lmm_INMA_interaction_sex_exposure.R, lines 1–60 · score 0.87 · sex interaction, maternal origin, nursery attendance, passive smoking, maternal education, maternal age
- [3] § Discovery analysis in the INMA-Sabadell cohort ↔ scripts/7_EWAS_BiSC_hormones_neuro.R, lines 1–71 · score 0.86 · missForest, nursery attendance, passive smoking, maternal education, maternal age, covariate
- [4] § Cross-cohort consistency analysis ↔ scripts/6_lmm_INMA_interaction_sex_exposure.R, lines 1–60 · score 0.85 · lmerTest, maternal BMI, nursery attendance, passive smoking, maternal education, maternal age
- [5] § Neurodevelopmental outcome assessments in children › INMA-Sabadell cohort ↔ scripts/3_lmm_INMA_hormones_neuro_with_residuals.R, lines 140–215 · score 0.59 · early motor skills, Early cognitive skills, general cognition, Mental, residuals
Paper
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The authors' code
R · 273 lines · 12 KB · no license · 2 matches
- # ====================================================================================================================================================================
- # Secondary analysis in the BiSC cohort: Linear regression models between prenatal steroid hormone exposures and early-life neurodevelopmental outcomes at 18 months
- # Author: Estelle Renard-Dausset
- # Purpose: Generate results table for the Exposure-Wide Association Study (EWAS) in BiSC
- # Requirements: dplyr, readxl, broom, gridExtra, tidyr, forcats
- # ====================================================================================================================================================================
- # Load libraries
- library(dplyr)
- library(readxl)
- library(broom)
- library(gridExtra)
- library(tidyr)
- library(forcats)
- # Load data
- codebook <- read.csv("data/codebook_BiSC_hormones.csv")
- data <- read.csv("data/data_IGRO_BiSC.csv")
- imputed_data <- read.csv("data/imputed_data_IGRO_BiSC.csv") # version where the covariates are imputed with missForest
- # Convert some variables to factor (categories)
- as_factor_cols <- c("educ_level_m_3cat", "hosp_recruit_m_12w", "ethnicity_m_3cat","b_sexo", "ethnicity_m", "parity_m", "parity_m_2cat",
- "S17", "smoke_any_m", "smoke_sust_m", "BISC_cb_v01_12w_questMareEV12w.smokepassive_m_preg_2c",
- "d1_diet.breastfeeding.yn_c_18m_3c", "o5_nursery_c_18m_4c",
- "nursery_18m", "smoke_pregnancy", "breastfeeding_18m", "maternal_ethnicity","maternal_education")
- data <- data %>% mutate(across(all_of(as_factor_cols), as.factor))
- imputed_data <- imputed_data %>% mutate(across(all_of(as_factor_cols), as.factor))
- # nursery_18m, smoke_pregnancy, breastfeeding_18m, maternal_ethnicity, maternal_education --> New categorical vars
- # EARLY-LIFE NEURODEVELOPMENTAL OUTCOMES
- # Cognitive direct score: bay_pdg_c_18m
- # Receptive communication direct score: bay_pdcr_c_18m
- # Expressive communication direct score:bay_pdce_c_18m
- # Fine motor skills direct score: bay_pdmf_c_18m
- # Gross motor skills direct score: bay_pdmg_c_18m
- outcomes <- c("bay_pdg_c_18m", "bay_pdcr_c_18m", "bay_pdce_c_18m", "bay_pdmf_c_18m", "bay_pdmg_c_18m")
- # Scale scores: transform to mean of 10 and standard deviation is 3
- imputed_data <- imputed_data %>%
- mutate(
- bay_pdg_c_18m_scaled = 10 + 3 * (bay_pdg_c_18m - mean(bay_pdg_c_18m, na.rm = TRUE)) / sd(bay_pdg_c_18m, na.rm = TRUE),
- bay_pdcr_c_18m_scaled = 10 + 3 * (bay_pdcr_c_18m - mean(bay_pdcr_c_18m, na.rm = TRUE)) / sd(bay_pdcr_c_18m, na.rm = TRUE),
- bay_pdce_c_18m_scaled = 10 + 3 * (bay_pdce_c_18m - mean(bay_pdce_c_18m, na.rm = TRUE)) / sd(bay_pdce_c_18m, na.rm = TRUE),
- bay_pdmf_c_18m_scaled = 10 + 3 * (bay_pdmf_c_18m - mean(bay_pdmf_c_18m, na.rm = TRUE)) / sd(bay_pdmf_c_18m, na.rm = TRUE),
- bay_pdmg_c_18m_scaled = 10 + 3 * (bay_pdmg_c_18m - mean(bay_pdmg_c_18m, na.rm = TRUE)) / sd(bay_pdmg_c_18m, na.rm = TRUE)
- )
- scaled_outcomes <- c("bay_pdg_c_18m_scaled", "bay_pdcr_c_18m_scaled", "bay_pdce_c_18m_scaled", "bay_pdmf_c_18m_scaled", "bay_pdmg_c_18m_scaled")
- # Compute age in number of days at Bayley test:
- imputed_data$age_bayley_days <- imputed_data$bay_date.d_c_18m + (imputed_data$bay_date.m_c_18m * 30.4368) + (imputed_data$bay_date.y_c_18m * 365.2422)
- model_number <- "model_1" #"model_1" #model_2
- confounders <- switch(model_number,
- # Model 1 = Total effect: Maternal age, maternal education, maternal ethnicity, maternal BMI 12w, parity, smoking,
- # passive smoking, sex of the child, age at Bayley test, nursery attendance
- "model_5" = c("edad", "maternal_education", "maternal_ethnicity", "bmi_m_12w", "parity_m_2cat", "smoke_pregnancy",
- "BISC_cb_v01_12w_questMareEV12w.smokepassive_m_preg_2c", "b_sexo", "age_bayley_days", "nursery_18m"),
- # Model 2 = Direct effect: Maternal age, maternal education, maternal ethnicity, maternal BMI 12w, parity, smoking,
- # passive smoking, sex of the child, age at Bayley test, nursery attendance, breastfeeding status
- "model_6" = c("edad", "maternal_education", "maternal_ethnicity", "bmi_m_12w", "parity_m_2cat", "smoke_pregnancy",
- "BISC_cb_v01_12w_questMareEV12w.smokepassive_m_preg_2c", "b_sexo", "age_bayley_days", "nursery_18m", "breastfeeding_18m"),
- stop("Invalid model number")
- )
- # Formula for EWAS (Exposure-Wide Association Study)
- define_formula <- function(outcome, exposure, confounders, log2=FALSE) {
- if(log2 ==TRUE){
- return(as.formula(paste(outcome, "~", "log2(",exposure, ") +", paste(confounders, collapse = " + "))))
- }
- else{return(as.formula(paste(outcome, "~", exposure, " +", paste(confounders, collapse = " + "))))
- }
- }
- # Compute effective number of tests for specific columns of the dataset (ENT)
- # Input: data for which to compute ENT
- # Output: Effective Number of Tests
- compute_ENT <- function(data_ENT) {
- cor_matrix <- cor(data_ENT, use = "pairwise.complete.obs") #Compute the correlation matrix
- eigen_values <- eigen(cor_matrix)$values #Perform eigenvalue decomposition
- ENT <- sum(pmin(eigen_values, 1)) #Calculate the effective number of tests
- return(ENT)
- }
- # PREDICTORS
- # 1 - Hormone metabolites
- hormones <- imputed_data %>% select(ends_with("32w_i_SG_GA_adj")) %>% colnames()
- # 2 - Hormone sums
- sum_hormones <- grep("^sum_.*SG_GA_adj$", colnames(imputed_data), value=TRUE)
- # 3 - Sulfate/Glucuronide ratios
- ratios_SG <- grep("ratio_SG_.*_GA_adj$", colnames(imputed_data), value=T)
- ratios_SG <- ratios_SG[!grepl("_SG_GA_adj$", ratios_SG)]
- # 4 - Phase I (product/precursor) ratios
- ratios_phaseI <- imputed_data %>% select(starts_with("ratio")& !starts_with("ratio_SG") & ends_with("_GA_adj")) %>% colnames()
- ratios_phaseI <- ratios_phaseI[!grepl("_SG_GA_adj$", ratios_phaseI)]
- predictors <- c(hormones, sum_hormones, ratios_SG, ratios_phaseI)
- # Compute ENT
- ENT_hormones <- compute_ENT(imputed_data[,hormones])
- ENT_sums <- compute_ENT(imputed_data[,sum_hormones])
- ENT_SG_ratios <- compute_ENT(imputed_data[,ratios_SG])
- ENT_phase_I_ratios <- compute_ENT(imputed_data[,ratios_phaseI])
- ENT_outcomes <- compute_ENT(imputed_data[,scaled_outcomes])
- #### EWAS ####
- results_df_hormones <- data.frame()
- results_df_sums <- data.frame()
- results_df_SG_ratio <- data.frame()
- results_df_phaseI_ratio <- data.frame()
- for(outcome in scaled_outcomes) {
- #### 1 - Hormone metabolites ####
- for(hormone in hormones) {
- # Keep only participants with available outcome, hormone and confounder data:
- cols <- c(outcome, hormone, confounders)
- filtered_df <- imputed_data[complete.cases(imputed_data[,cols]),]
- n <- nrow(filtered_df)
- formula <- define_formula(outcome, hormone, confounders, log2 = TRUE)
- model <- lm(formula, data=filtered_df)
- r2_full <- summary(model)$r.squared
- formula_conf <- as.formula(paste(outcome, "~", paste(confounders, collapse = " + ")))
- model_conf <- lm(formula_conf, data = filtered_df)
- r2_conf <- summary(model_conf)$r.squared
- # Variance explained by the predictor alone
- r2_predictor <- r2_full - r2_conf
- results <- tidy(model, conf.int = TRUE, conf.level = 0.95) %>%
- mutate(outcome = outcome,
- predictor = hormone,
- sample_size = n,
- R2_predictor = r2_predictor,
- R2_full = r2_full,
- signif_thresh = 0.05/(ENT_hormones * ENT_outcomes),
- model = model_number)
- log2_hormone <- paste0("log2(",hormone,")")
- results <- results %>% filter(term == log2_hormone)
- results_df_hormones <- rbind(results_df_hormones, results)
- }
- #### 2 - Hormone sums ####
- for(sum in sum_hormones) {
- # Keep only participants with available outcome, sum hormone and confounder data
- # Remove rows where the sum is zero:
- # Due to a few missing values of Gestational Age, we have NA in GA_adj hormones for some participants,
- # Therefore the sum is zero and becomes infinite after log2 transform
- cols <- c(outcome, sum, confounders)
- filtered_df <- imputed_data[imputed_data[[sum]] != 0 & complete.cases(imputed_data[,cols]),]
- n <- nrow(filtered_df)
- log2_sum <- paste0("log2(",sum,")")
- formula <- define_formula(outcome, sum, confounders, log2 = TRUE)
- model <- lm(formula, data=filtered_df)
- r2_full <- summary(model)$r.squared
- formula_conf <- as.formula(paste(outcome, "~", paste(confounders, collapse = " + ")))
- model_conf <- lm(formula_conf, data = filtered_df)
- r2_conf <- summary(model_conf)$r.squared
- # Variance explained by the predictor alone
- r2_predictor <- r2_full - r2_conf
- results <- tidy(model, conf.int = TRUE, conf.level = 0.95) %>%
- mutate(outcome = outcome,
- predictor = sum,
- sample_size = n,
- R2_predictor = r2_predictor,
- R2_full = r2_full,
- signif_thresh = 0.05/(ENT_sums * ENT_outcomes),
- model = model_number)
- results <- results %>% filter(term == log2_sum)
- results_df_sums <- rbind(results_df_sums, results)
- }
- #### 3 - Sulfate/Glucuronide ratios ####
- for(ratio in ratios_SG) {
- # Keep only participants with available outcome, ratio hormone and confounder data:
- cols <- c(outcome, ratio, confounders)
- filtered_df <- imputed_data[complete.cases(imputed_data[,cols]),]
- n <- nrow(filtered_df)
- formula <- define_formula(outcome, ratio, confounders, log2 = TRUE)
- model <- lm(formula, data=filtered_df)
- r2_full <- summary(model)$r.squared
- formula_conf <- as.formula(paste(outcome, "~", paste(confounders, collapse = " + ")))
- model_conf <- lm(formula_conf, data = filtered_df)
- r2_conf <- summary(model_conf)$r.squared
- # Variance explained by the predictor alone
- r2_predictor <- r2_full - r2_conf
- results <- tidy(model, conf.int = TRUE, conf.level = 0.95) %>%
- mutate(outcome = outcome,
- predictor = ratio,
- sample_size = n,
- R2_predictor = r2_predictor,
- R2_full = r2_full,
- signif_thresh = 0.05/(ENT_SG_ratios * ENT_outcomes),
- model = model_number)
- log2_ratio <- paste0("log2(",ratio,")")
- results <- results %>% filter(term == log2_ratio)
- results_df_SG_ratio <- rbind(results_df_SG_ratio, results)
- }
- #### 4 - Phase I ratios ####
- for(ratio in ratios_phaseI) {
- # Keep only participants with available outcome, ratio hormone and confounder data:
- cols <- c(outcome, ratio, confounders)
- filtered_df <- imputed_data[complete.cases(imputed_data[,cols]),]
- n <- nrow(filtered_df)
- formula <- define_formula(outcome, ratio, confounders, log2 = TRUE)
- model <- lm(formula, data=filtered_df)
- r2_full <- summary(model)$r.squared
- formula_conf <- as.formula(paste(outcome, "~", paste(confounders, collapse = " + ")))
- model_conf <- lm(formula_conf, data = filtered_df)
- r2_conf <- summary(model_conf)$r.squared
- # Variance explained by the predictor alone
- r2_predictor <- r2_full - r2_conf
- results <- tidy(model, conf.int = TRUE, conf.level = 0.95) %>%
- mutate(outcome = outcome,
- predictor = ratio,
- sample_size = n,
- R2_predictor = r2_predictor,
- R2_full = r2_full,
- signif_thresh = 0.05/(ENT_phase_I_ratios * ENT_outcomes),
- model = model_number)
- log2_ratio <- paste0("log2(",ratio,")")
- results <- results %>% filter(term == log2_ratio)
- results_df_phaseI_ratio <- rbind(results_df_phaseI_ratio, results)
- }
- }
- EWAS_results <- rbind(results_df_hormones, results_df_sums, results_df_SG_ratio, results_df_phaseI_ratio)
- EWAS_results <- merge(EWAS_results, codebook %>% select(variable, variable_group, variable_plot_name, hormone_full_name, hormone, hormone_group, sum_hormone_group), by.x= "predictor", by.y="variable", all.x=T)
- write.csv(EWAS_results, file= paste0("results/",model_number,"/result_files/EWAS_results_", model_number,".csv"), row.names=FALSE)
7_EWAS_BiSC_hormones_neuro.R at commit 52599f3, no license · at the source
Overview
- Barcelona Institute for Global Health
- Hospital del Mar Medical Research Institute
- Hospices Civils de Lyon
Abstract
Background: Neurodevelopmental disorders affect millions of children worldwide, yet their prenatal biological origins remain unclear. Steroid hormones regulate key processes in fetal brain development, but the role of maternal steroid metabolism during pregnancy on children's neurodevelopment remains poorly understood.
Methods: We report the first comprehensive longitudinal analysis of maternal steroid metabolism in late pregnancy in relation to offspring neurodevelopment. We quantified 50 maternal urinary steroid metabolites and derived 40 indicators of steroid metabolism in third-trimester samples from two Spanish birth cohorts (INMA-Sabadell, n = 500; BiSC, n = 556). In INMA-Sabadell, child cognition, motor development, attention and behaviour were assessed repeatedly from 15 months to 15 years, and associations were estimated using linear mixed-effects models, including sex-stratified analyses. As a secondary analysis, we evaluated cross-cohort consistency by testing whether associations with early- life cognitive and motor outcomes identified in INMA-Sabadell were also observed in BiSC at 18 months using linear regression models.
Results: In INMA-Sabadell, higher maternal levels of the cortisol metabolite 20α-dihydrocortisol-gluc
Conclusions: These findings establish maternal steroid metabolism as a determinant of child neurodevelopment, highlight the relevance of including metabolic transformation indicators, and identify both shared and sex-specific in utero biomarkers of neurodevelopmental trajectories.
Reproduced under the paper's license (CC BY), from the paper cited above.
Repository
Its files are read in the Code ↔ Paper reader above, with 5 matches between paragraphs and lines of code.
EstelleRD/prenatal-steroids-neurodevelopment
52599f385c8f38156f2e110e254e80cee2075edc, 27 January 2026Availability: 1 check, the latest on 29 September 2026: the link answers
- 29 September 2026: the link answers
8 files
- scripts/
1_create_longitudinal_da , R, 243 linestasets_INMA.R - scripts/
2_lmm_INMA_hormones_neur , R, 340 lineso.R - scripts/
3_lmm_INMA_hormones_neur , R, 426 lines, 1 matcho_with_residuals.R - scripts/
4_lmm_sex_stratified_INM , R, 513 linesA_hormones_neuro.R - scripts/
5_lmm_sex_stratified_INM , R, 689 linesA_hormones_neuro_with_re siduals.R - scripts/
6_lmm_INMA_interaction_s , R, 418 lines, 2 matchesex_exposure.R - scripts/
7_EWAS_BiSC_hormones_neu , R, 273 lines, 2 matchesro.R - README.md, Text, 21 lines
The paper's code and data availability statement is in the Data section.
Tracing map
Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.
What the map holds:
- 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
- 7 scripts, each with its path and the digest of its content;
- 5 matches between paragraphs of the paper and lines of the code (method lexical-v1);
- neither the text of the paper nor the code itself.
Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.
Data
No dataset and no data link were found in the paper.
Availability of data and materials
The participants data reported in this study cannot be deposited in a public repository due to participant confidentiality and privacy concerns. Therefore, data is available upon written request. According to standard controlled access procedure, applications to use the BiSC and INMA-Sabadell data will be reviewed by the Steering Committee, evaluation of the fit of the data for the proposed methodology, and verification that the proposed use meets the guidelines of the Ethic and Governance Framework and of the consent that was provided by the participants. To request BiSC data follow the instructions described in the website.
All original analytical code has been deposited in a GitHub repository and is publicly available at https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 29 September 2026: the first record
Recorded: type, journal, dates, 12 authors, 6 keywords, 42 references.
Cite
This paper
Renard-Dausset, E., Laveriano-Santos, E. P., Bustamante, M., Ferrer, M., Gascon, M., Guxens, M., Haro, N., Julvez, J., Portefaix, A., Vrijheid, M., Pozo, Ó. J., & Maitre, L. (2026). Prenatal exposure to maternal steroid hormones and child neurodevelopment: evidence for sex-specific effects in a longitudinal birth cohort. Research Square (preprint). https://
BibTeX
@article{renarddausset20
author = {Renard-Dausset, Estelle and Laveriano-Santos, Emily P. and Bustamante, Mariona and Ferrer, Muriel and Gascon, Mireia and Guxens, Mònica and Haro, Noemí and Julvez, Jordi and Portefaix, Aurélie and Vrijheid, Martine and Pozo, Óscar J and Maitre, Léa},
title = {{Prenatal exposure to maternal steroid hormones and child neurodevelopment: evidence for sex-specific effects in a longitudinal birth cohort}},
journal = {Research Square (preprint)},
year = {2026},
month = apr,
publisher = {Research Square},
issn = {2693-5015},
doi = {10.21203/
url = {https://
}
RIS
TY - JOUR
AU - Renard-Dausset, Estelle
AU - Laveriano-Santos, Emily P.
AU - Bustamante, Mariona
AU - Ferrer, Muriel
AU - Gascon, Mireia
AU - Guxens, Mònica
AU - Haro, Noemí
AU - Julvez, Jordi
AU - Portefaix, Aurélie
AU - Vrijheid, Martine
AU - Pozo, Óscar J
AU - Maitre, Léa
TI - Prenatal exposure to maternal steroid hormones and child neurodevelopment: evidence for sex-specific effects in a longitudinal birth cohort
T2 - Research Square (preprint)
J2 - Res Sq
PY - 2026
DA - 2026/
SN - 2693-5015
PB - Research Square
DO - 10.21203/
UR - https://
ER -
CSL-JSON
{
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"type": "article",
"title": "Prenatal exposure to maternal steroid hormones and child neurodevelopment: evidence for sex-specific effects in a longitudinal birth cohort",
"container-title": "Research Square (preprint)",
"author": [
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"family": "Renard-Dausset",
"given": "Estelle"
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"family": "Laveriano-Santos",
"given": "Emily P."
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"given": "Aurélie"
},
{
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{
"family": "Pozo",
"given": "Óscar J"
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"given": "Léa"
}
],
"container-title-short":
"DOI": "10.21203/
"ISSN": "2693-5015",
"publisher": "Research Square",
"URL": "https://
"issued": {
"date-parts": [
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}
}
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