A Cohort Study on the Impact of Gestational Blood Glucose Management and Postnatal Nurturing Environment on Delayed Language Development in Children
Conditions: Gestational Diabetes Mellitus in Pregnancy, Cognitive Impairment, Cohort Study
Sponsor: Gansu Provincial Maternal and Child Health Care Hospital

Medical Ethics Committee of Gansu PMCH                           Version 1.0  Date: April 20th,2023   
 
 
Gansu Provincial Maternity and Childcare Hospital  
Statistical Analysis Plan (SAP)  
 
 
 
Project name:  A cohort study on the effects of gestational blood sugar         
         management and postnatal nurturing environment on      
 delayed language development in children 
Project source: National Clinical Medical Research Center for  
Child Health and Disease                            
Responsible person:  Yanxia Wang                                         
Department:        Research Center                                      
Principal Investigator: Yanxia Wang                                        
Research period:     December 2022 to November 2025               
 
 
 
 
Version number: 1.0.      Date of version: April 20th, 2023 
 
 
 
 
 

Medical Ethics Committee of Gansu PMCH                           Version 1.0  Date: April 20th,2023   
 
According to the implementation plan of the "Western Baby Plan" 
queue, 1.5-2.5-year-old offspring children who have entered the "Western 
Baby Plan" queue as research objects were be surveyed. The language 
development and family nurturing environment of 2-year-old children 
using the "Language Development Evaluation S-S Method, Gesell Infant 
and Toddler Development Scale, and 0-6 Year Old Family Nurturing 
Environment Evaluation Scale" were be evaluated. We investigated the 
results of blood sugar screening during pregnancy of children's mothers 
using retrospective cohort study methods, and follow up the blood sugar 
management effect of pregnant women with abnormal blood sugar before 
delivery. At the same time, pregnant women diagnosed with abnormal 
blood sugar during pregnancy are used as research objects to conduct 
prospective cohort studies: collect standardized epidemiological survey 
data of the "Western Baby Plan" queue (mainly including general 
conditions, diet, exercise, environmental factor investigations, etc.), follow 
up blood sugar control methods at 36-40 weeks of pregnancy, record pre-
pregnancy blood sugar control results and neonatal outcomes, collect 
peripheral blood and umbilical blood during delivery and store them in the 
mother-infant biological sample library. The study would follow up the 
growth and development of offspring, and evaluate the language 
development and family nurturing environment of 2-year-old children 
using the "Language Development Evaluation S-S Method, Gesell Infant 
and Toddler Development Scale, and 0-6 Year Old Family Nurturing 
Environment Evaluation Scale". 
Sample size estimation: Referring to delayed language development 
in children as the disease outcome, the incidence rate (p1) of delayed 
language development in the group exposed to high prenatal sugar is 15%, 
and the relative risk (RR) is 2.0, with a desired significance level (a) of 
0.05 and a desired power (1-b) of 0.90. By plugging in these values into 

Medical Ethics Committee of Gansu PMCH                           Version 1.0  Date: April 20th,2023   
 
the formula, it is determined that both the exposed group and the control 
group require 160 individuals. Considering the possibility of loss to follow-
up, the sample size is increased by 10%. The final estimated sample size 
for the cohort is 356 cases, with a planned investigation of 360 individuals 
in the blood sugar abnormality specialized disease cohort.  
The sample calculation formula for the cohort study collects data 
information through the electronic medical record system and the Western 
Children's Health and Disease Cohort Platform, with dual data entry into 
an Excel database. Differences in the distribution of general conditions of 
pregnant women are compared using statistical methods such as the chi-
square test or Fisher's exact probability test for categorical data (Socio 
demographic profile, menstrual and reproductive history, indoor 
environment Environmental factors, Scale indicators etc.), and statistical 
methods such as the t-test or ANOVA test for continuous data (Check labs 
(e.g., fasting blood glucose, glycosylated hemoglobin, lipids, liver and 
kidney function, etc.). After further controlling for confounding factors, 
logistic regression analysis is used to explore the impact of poor blood 
sugar management (high prenatal sugar exposure) on delayed language 
development around 1-2 years of age.  
The combined effect of GDM and postnatal environment of the 
offspring was analyzed using an EXCEL spreadsheet developed by 
Andersson et al. The additive interaction was evaluated using three indices: 
relative excess risk due to interaction (RERI), attributable proportion due 
to interaction (AP), and synergy index (S). If the 95% confidence intervals 
(CI) of RERI and AP included 0, and the 95% CI of S included 1, it 
indicated no additive interaction; otherwise, there was an additive 
interaction.  
The regression models were used to screen the effect of maternal 
GDM and related factors on the delayed language development (DLD) in 

Medical Ethics Committee of Gansu PMCH                           Version 1.0  Date: April 20th,2023   
 
offspring. The binomial logistics regression model and the lasso regression 
model were constructed by using the "rms" and "glmnet" package to 
analyse risk factors. The nomogram, which based on proportionally 
converting each regression coefficient to a zero to one-hundred-point scale, 
was used to screen the effect of maternal GDM and related factors on the 
DLD. The effect of the variable with the highest β coefficient was assigned 
one hundred points. The points were added across independent variables to 
derive total points, which were converted to predicted probabilities. The 
total scores of each patient were calculated based on the nomogram for 
clinical prediction. We used the predictive performance of the nomogram 
was measured by concordance index (C index). Prediction models were 
validated by plotting calibration curves and using bootstrap method with 
one thousand replicate samples. The clinical validity of the prediction 
model was evaluated using decision curve analysis (DCA).  
All analyses were performed using SPSS software (SPSS Inc., 
Chicago, IL, USA, version 21.0) and R version (4.1.3, http://www.r-
project.org/). The significance level for statistical tests is set at a value of 
0.05, the selection criterion for the regression equation is set at a level of 
0.05, and the exclusion level is set at 0.10. Missing values are handled 
according to the default method in SPSS, which means that observations 
with missing values in the test variables are excluded from the analysis. A 
p-value of <0.05 indicates a statistically significant difference.