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This birth cohort study recruited mothers after childbirth who had their first postnatal check-ups at two District Women and Children Health and Family Planning Service Centers in Tianjin, China, between July 2015 and March 2017. The investigators collected and measured the developmental status of the child at 1, 12, and 24 months of age. As of May 2018, there were 2,563 mother-child pairs with follow-up visits. According to previous literatures, participant information was collected via questionnaires at the first postnatal check-ups, including maternal age (in years), education level, family monthly income (Chinese Yuan, CNY), smoking and alcohol consumption during pregnancy, gestation weeks, delivery pattern, parity, height (cm), pre-pregnancy weight (kg), antenatal weight (kg), and birth weight of the newborn. Women were excluded if they self-reported having gestational diabetes, pre-eclampsia or poor birth outcomes, or used drugs during pregnancy. Finally, 2,253 mother-child pairs were included in this study. All participants provided informed consent in writing. The protocol of this study was approved by the Ethics Committee of the Tianjin Medical University (No. 2015005).
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Pre-pregnancy BMI is calculated by dividing maternal pre-pregnancy weight (in kg) by height (in m) squared, and is universally expressed in units of kg/m2[20, 21]. Maternal pre-pregnancy weight and height were collected via questionnaires at the first postnatal check-ups. The data was confirmed by reference to medical records during pregnancy, which listed maternal weight and height at their mother’s first pre-natal visit. The 2,253 women in this study were grouped by BMI, using the cut-offs recommended by the WHO: 1,871 women with BMI < 25 kg/m2, 323 overweight women (25 kg/m2 ≤ BMI < 30 kg/m2), and 59 women with obesity (BMI ≥ 30 kg/m2). The sample size of obesity was very small, and the uneven sample sizes of the different BMI groups could have affected the reliability of the results. Thus, overweight and obesity were combined into one group (BMI ≥ 25 kg/m2), and BMI < 25 kg/m2 was defined as a healthy range for reference[18, 22, 23]. The associations between pre-pregnancy BMI and offspring neuropsychological development were systematically analyzed by BMI class (BMI < 25 kg/m2 and BMI ≥ 25 kg/m2).
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The China Developmental Scale for Children, which was published by the Capital Pediatrics Research Institute in China, has been used to assess the developmental quotients (DQs) children aged 0-6 years since 1980[24, 25]. As the first standardized instrument for assessing the neuropsychological development of children in China, Cronbach’s α for the reliability is 0.91, and the scale is highly correlated with the Gesell Developmental Schedule, with a correlation coefficient of 0.954[26, 27]. This scale has proven reliable and practical in clinical practice for the intelligent diagnosis of infants and young children. For decades, the scale has been used for the early identification and quantification of developmental delay and to determine eligibility for early intervention services for infants in China. It is of great utility for improving rehabilitation opportunities[24, 27].
The China Developmental Scale for Children allows differential diagnosis of initial suspicions of developmental disorder by providing independent standard scores for different scales and subtests (gross motor, fine motor, adaptive, language, and social). Specifically, motor behavior (gross motor and fine motor) includes balance, walking, and hand control; adaptive behavior includes imitation, discriminative performance, and perception; language behavior is assessed in terms of vocabulary, word comprehension, and conversation; and social behavior includes reactions to persons, personal habits, and acquired information. For infants at 1 month of age, this scale consists of six items organized into one gross motor item, one fine motor item, two adaptive items, one language item, and one social behavior item; for infants at 12 months of age, there are eight items organized into two gross motor items, two fine motor items, one adaptive item, two language items, and one social behavior item; for infants at 24 months of age, there are seven items organized into one gross motor item, one fine motor item, two adaptive items, two language items, and one social behavior item. The raw scores can be transformed into DQ [total DQ = (raw scores of five domains/5/current age in months) × 100]. Then, children can be classified as outstanding (total DQ scores ≥ 130), well developed (total DQ scores 115-129), normal (total DQ scores 85-114), moderately delayed (total DQ scores 70-84), or severely delayed (total DQ scores < 70)[26, 27].
In this study, one pediatrician estimated the current neurodevelopment age (expressed in months) for each of the five specific domains, which were also adjusted by month age to ensure comparability among individuals. To ensure that the five domains and total DQ could be represented in the same graph, the five domains were adjusted by an order of magnitude, i.e., multiplied by 100. In the present study, the neurodevelopmental test was conducted at 1-, 12-, and 24-month-old by trained pediatricians in a quiet room of the District Women and Children Health and Family Planning Service Centre and in the presence of a parent. To minimize examiner variability, every effort was made to maximize reliability of scoring by performing standardized training procedures and regular self-checking.
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The sample size for the average time difference was calculated as follows:
$$ M = \frac{{{{\left( {{z_{1 - \alpha /2}} + {z_{1 - \beta }}} \right)}^2}\left[ {1 + \left( {n - 1} \right)\rho } \right]{s^2}}}{{n\left( {1 - \pi - {\pi ^2}} \right){d^2}}}{\text{,}^{[28]}} $$ Where α is the type I error rate, β is the type II error rate, s is the estimate of the standard deviation, d is the smallest meaningful time-averaged difference to be detected, n is the number of repeated observations per subject, ρ is the correlation between measures within an individual, m1 and m2 are the number of subjects in BMI ≥ 25 kg/m2 group and BMI < 25 kg/m2 group, respectively, π is the proportion of subjects within group 1 (m1/M) and M is the total number of subjects in the design.
By entering the parameter values (α = 0.05, β = 0.1, power = 1-β = 0.9, s = 20, d = 0.5, n = 3, ρ = 0.8, π = 30%) into the formula, sample size was obtained as follows: M = m1 + m2 = 276; m1 (BMI ≥ 25 kg/m2 group) = πM = 83; m2 (BMI < 25 kg/m2 group) = (1−π)M = 193. Assuming sample attrition of 30%, the sample size was increased to 359, with m1 (BMI ≥ 25 kg/m2 group) = 108 and m2 (BMI < 25 kg/m2 group) = 251; the samples collected in this study were larger than the estimated values.
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Statistical analysis was performed using Statistical Analysis System (SAS) version 9.4 software. Values were presented as means and standard deviations (SDs). Categorical variables were presented as n (%). Histograms were used to describe the DQ at different time points within different maternal pre-pregnancy BMI groups. ANOVA, Kruskal-Wallis, and Chi-square tests were used to compare the characteristics of the enrolled children and mothers between pre-pregnancy BMI groups. The significance level for all tests was P < 0.05 (two-tailed).
Mixed models[29] were used to explore the associations between child DQ and pre-pregnancy BMI. The number of months of follow-up in this study differed among individuals (Table 1); mixed models can accommodate unbalanced data patterns and use all available observations in the analysis. In this study, a mixed model was used to analyze how offspring neuropsychological development from 1 to 24 months was affected by the interaction between the mother’s pre-pregnancy BMI and the child’s age. Selected potential confounders were entered as covariates, including mother's age, change in BMI during pregnancy (∆BMI), education level, family monthly income, whether the mother smoked or consumed alcohol before or during pregnancy, delivery pattern, gestation weeks, parity, and child's sex and birth weight. The significance level for all tests was P < 0.05 (two-tailed). Post-hoc analysis with Sidak correction for multiple comparisons was used to assess differences in child DQ between the maternal pre-pregnancy BMI groups at each age (1, 12, and 24 months).
Age (mo) n (%) Total BMI < 25 kg/m2 BMI ≥ 25 kg/m2 1 1,623 (82.51) 344 (17.49) 1,967 12 1,091 (80.64) 262 (19.36) 1,353 24 398 (76.10) 125 (23.90) 523 Table 1. The sample size of offspring with different maternal pre-pregnancy BMI groups at eachfollow-up period
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Maternal and offspring characteristics at birth for the 2,253 mother-child pairs included in the study are listed in Table 2. The mean age of mothers was 31.04 ± 4.08 years (range 18-45 years). The mean pre-pregnancy BMI of mothers was 21.88 ± 3.42 kg/m2; pre-pregnancy BMI ≥ 25 kg/m2 was present in 16.96% of the mothers. The group with BMI < 25 kg/m2 was slightly younger than the group with pre-pregnancy BMI ≥ 25 kg/m2 (P < 0.001). Mothers with pre-pregnancy BMI ≥ 25 kg/m2 had lower ∆BMI, education, and family income, and higher baby birth weight (P < 0.001). Additionally, mothers in the group with BMI ≥ 25 kg/m2 were more often multiparity and a higher rate of cesarean section compared to the group with BMI < 25 kg/m2 (P < 0.05).
Variables BMI < 25 kg/m2 BMI ≥ 25 kg/m2 Total Pa (n = 1,871) (n = 382) (n = 2,253) Age (y) 30.89 ± 4.01b 31.08 ± 4.28 31.04 ± 4.08 < 0.001 Pre-pregnancy BMI (kg/m2) 20.69 ± 2.15 27.72 ± 2.29 21.88 ± 3.42 < 0.001 ∆BMI (kg/m2) 6.04 ± 2.14 4.44 ± 2.63 5.77 ± 2.31 < 0.001 Gestational Age (weeks) 38.93 ± 1.53 38.83 ± 1.86 38.91 ± 1.59 0.238 Birth Weight (kg) 3.35 ± 0.44 3.47 ± 0.51 3.37 ± 0.46 < 0.001 Gender, n (%) 0.779 Male 973 (52.0) 202 (52.9) 1,175 Female 898 (48.0) 180 (47.1) 1,078 Maternal education level, n (%) < 0.001 Low 229 (12.2) 64 (16.8) 293 Intermediate 1,432 (76.5) 295 (77.2) 1,727 High 210 (11.2) 23 (6.0) 233 Family monthly income (CNY), n (%) < 0.001 < 5,000 450 (24.1) 122 (31.9) 572 5,000- 899 (48.0) 188 (49.2) 1,087 > 10,000 522 (27.9) 72 (18.9) 594 Delivery pattern, n (%) 0.005 Natural delivery 1,036 (55.4) 181 (47.4) 1,217 Cesarean delivery 835 (44.6) 201 (52.6) 1,036 Parity, n (%) 0.003 Primiparity 1,297 (69.3) 235 (61.5) 1,532 Multiparity 574 (30.7) 147 (38.5) 721 Smoking during pregnancy, n (%) 0.343 Nonusers 1,843 (98.5) 379 (99.2) 2,222 Smokers 28 (1.5) 3 (0.8) 31 Alcohol consumption during pregnancy, n (%) 0.393 Nonusers 1,726 (92.3) 358 (93.7) 2,084 Alcohol consumers 145 (7.7) 24 (6.3) 169 Note. aANOVA, Kruskal Wallis and Chi-square test were used to compare the characteristics of the enrolled children and mothers between pre-pregnancy BMI groups. bData represent $\bar x \pm s $ (all such values). BMI, body mass index; ∆BMI, change in BMI during pregnancy; CNY, China Yuan. Table 2. Characteristics of the enrolled children & mothers in relation to pre-pregnancy BMI groups
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Table 3 shows fixed effects of age and pre-pregnancy BMI on offspring total DQ and five neurobehavioral domains. The mixed-model analysis revealed that pre-pregnancy BMI, month of age, and their interaction had significant effects on total DQ and five neurobehavioral domains after adjustment.
Neurobehavioral domains Pre-pregnancy BMI Age of month Pre-pregnancy BMI × Age of month F P F P F P Total DQ 20.99 < 0.001 586.60 < 0.001 22.63 < 0.001 Gross motor 1.31 < 0.001 228.00 < 0.001 8.95 < 0.001 Fine motor 1.06 < 0.001 153.70 < 0.001 9.40 < 0.001 Adaptive 11.45 < 0.001 231.80 < 0.001 7.01 < 0.001 Language 1.22 < 0.001 401.40 < 0.001 12.30 < 0.001 Social 8.73 < 0.001 472.50 < 0.001 14.29 < 0.001 Note. Adjusted for mother's age, education level, family monthly income, ∆BMI, gestational weeks, delivery pattern, parity, smoking and alcohol consumption, child's sex, birth weight. Table 3. Fixed effects of age and pre-pregnancy BMI on offspring total DQ and five neurobehavioral domains
The estimates and model are shown in Supplementary Table S1 (available in www.besjournal.com). In terms of the interaction, the estimate of pre-preg
nancy BMI ≥ 25 vs. < 25 kg/m2 at 12-month-age was significantly smaller than at 1-month-age for total DQ (β = −10.10, P < 0.001) and five neurobehavioral domains (gross motor: β = −10.31, P < 0.001; fine motor: β = −9, P < 0.001; adaptive: β = −8.9, P = 0.001; language: β = −11.56, P < 0.001; and social: β = −10.82, P < 0.001). The estimate of pre-pregnancy BMI ≥ 25 vs. < 25 kg/m2 at 24-month-age was also significantly smaller than at 1-month-age for total DQ (β = −12.42, P < 0.001) and five neurobehavioral domains (gross motor: β = −11.73, P < 0.001; fine motor: β = −10.87, P < 0.001; adaptive: β = −9.93, P < 0.001; language: β = −15.25, P < 0.001; and social: β = −13.42, P < 0.001). Variables Age of month BMI group Total DQ Gross motor Fine motor Adaptive Language Social β P β P β P β P β P β P Pre-pregnancy BMI < 25 kg/m2 Ref. Ref. Ref. Ref. Ref. Ref. Pre-pregnancy BMI ≥ 25 kg/m2 10.40 < 0.001 10.58 < 0.001 9.03 < 0.001 9.40 < 0.001 12.36 < 0.001 10.82 < 0.001 Age of month 1 Ref. Ref. Ref. Ref. Ref. Ref. Age of month 12 −23.77 < 0.001 −21.60 < 0.001 −14.34 < 0.001 −24.34 < 0.001 −29.88 < 0.001 −30.12 < 0.001 Age of month 24 −26.53 < 0.001 −22.16 < 0.001 −18.10 < 0.001 −25.09 < 0.001 −34.89 < 0.001 −34.07 < 0.001 Pre-pregnancy BMI × Age of month 1 ≥ 25 vs. <25 kg/m2 Ref. Ref. Ref. Ref. Ref. Ref. Pre-pregnancy BMI × Age of month 12 ≥ 25 vs. <25 kg/m2 −10.10 < 0.001 −10.31 < 0.001 −9.00 < 0.001 −8.90 0.001 −11.56 < 0.001 −10.80 < 0.001 Pre-pregnancy BMI × Age of month 24 ≥ 25 vs. <25 kg/m2 −12.42 < 0.001 −11.73 < 0.001 −10.87 < 0.001 −9.93 < 0.001 −15.25 < 0.001 −13.42 < 0.001 Note. Adjusted for mother's age, education level, family monthly income, ∆BMI, gestational weeks, delivery pattern, parity, smoking and alcohol consumption, child's sex, birth weight. Table S1. Estimates of fixed effects on offspring total DQ and five neurobehavioral domains
When pre−pregnancy BMI was used as a categorical variable, age × pre−pregnancy BMI ≥ 25 kg/m2 had a negative effect in comparison with age × pre−pregnancy BMI < 25 kg/m2 after adjustment (Figure 1) on total DQ (β = −0.56, 95% CI: −0.78 to −0.34, P < 0.001) and five neurobehavioral domains (gross motor: β = −0.53, 95% CI: −0.84 to −0.22, P < 0.001; fine motor: β = −0.56, 95% CI: −0.84 to −0.28, P < 0.001; adaptive: β = −0.46, 95% CI: −0.79 to −0.14, P < 0.005; language: β = −0.67, 95% CI: −1.00 to −0.34, P < 0.001; and social: β = −0.58, 95% CI: −0.88 to −0.27, P < 0.001).
Figure 1. Forest plots showing the age × pre-pregnancy BMI groups (BMI < 25 kg/m2 vs. BMI ≥ 25 kg/m2) interaction for total DQ and five neurobehavioral domains.○: crude model. ●: adjusted model for mother's age, education level, family monthly income, ∆BMI, gestational weeks, delivery pattern, parity, smoking and alcohol consumption, child's sex, birth weight. Reference variable was age × pre-pregnancy BMI < 25 kg/m2.
Post-hoc multiple comparisons revealed that children of mothers with pre-pregnancy BMI ≥ 25 kg/m2 were significantly higher in total DQ and five neurobehavioral domains (gross motor, fine motor, adaptive, language, and social) at 1 month of age in comparison with children of mothers with pre-pregnancy BMI < 25 kg/m2 (P < 0.05, Sidak-corrected). A completely opposite result was observed for DQ at 24 months of age, whereby maternal pre-pregnancy BMI ≥ 25 kg/m2 was associated with lower total DQ and five neurobehavioral domains (gross motor, fine motor, adaptive, language, and social) of children; statistically significant differences were found in total DQ and social neurobehavioral domains (P < 0.05). There was no significant difference in offspring neuropsychological development at 12 months of age between maternal pre-pregnancy BMI classes (BMI < 25 kg/m2 vs. BMI ≥ 25 kg/m2; Figure 2).
Figure 2. Multiple comparisons for total DQ and five neurobehavioral domains at each age between different maternal pre-pregnancy BMI groups. (A) 1-month-age DQ; (B) 12-month-age DQ; (C) 24-month-age DQ. Data are expressed as
$\bar x \pm s $ . *The significant difference in offspring neuropsychological development at each age between maternal pre-pregnancy BMI groups after adjusted for mother's age, education level, family monthly income, ∆BMI, gestational weeks, delivery pattern, parity, smoking and alcohol consumption, child's sex, birth weight (P < 0.05, Sidak-corrected).
Association between Pre-pregnancy Body Mass Index and Offspring Neuropsychological Development from 1 to 24 Months of Age: A Birth Cohort Study in China
doi: 10.3967/bes2019.093
- Received Date: 2019-04-25
- Accepted Date: 2019-09-16
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Key words:
- Pre-pregnancy BMI /
- Neuropsychological development /
- Offspring /
- The first 1,000 days /
- Birth cohort study
Abstract:
Citation: | CAO Lu Jia, LIN Hong Yan, LIANG Xuan, CHEN Yong Jie, LIU Yu Yan, ZHENG Yu Zhi, WANG Xin Yan, LI Wen, YAN Jing, HUANG Guo Wei. Association between Pre-pregnancy Body Mass Index and Offspring Neuropsychological Development from 1 to 24 Months of Age: A Birth Cohort Study in China[J]. Biomedical and Environmental Sciences, 2019, 32(10): 730-738. doi: 10.3967/bes2019.093 |