Department of Occupational and Environmental Health, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
Front Endocrinol (Lausanne). 2022 Jul 14;13:939366. doi: 10.3389/fendo.2022.939366. eCollection 2022.
Infants born small for gestational age (SGA) with no catch-up growth (No-CU) are at high risk of intellectual and developmental disabilities. However, factors leading to No-CU among SGA infants are unclear. This study aimed to examine the association between maternal total cholesterol (TC) in mid-pregnancy and No-CU at 3 years among full-term SGA infants.
The Japan Environment and Children's Study (JECS) is a nationwide prospective birth cohort study. We extracted a total of 2,222 mothers and full-term SGA infants (length and/or weight <-2 standard deviation [SD]) without congenital abnormalities from the original JECS cohort comprising a total of 104,062 fetal records. According to the distribution of maternal TC in the entire cohort, participants were classified into nine groups per each fifth percentile with the 20th-79th percentiles (204-260 mg/dl) as the reference group. No-CU was defined by a Z-score of height at 3 years <-2 SD according to the growth standard charts for Japanese children. Multivariable-adjusted logistic regression models were carried out using multiple imputations. Additionally, a multiple-adjusted restricted cubic spline model was performed in the complete dataset.
A total of 362 (16.3%) children were No-CU at 3 years. After adjusting for the Z-score of birth weight, age of mother, smoking status, weight gain during pregnancy, breastfeeding and meal frequency at 2 years, and parents' heights, the odds ratio (95% confidence intervals) of No-CU was 2.95 (1.28-6.80) for children whose maternal TC levels were in the highest category (≥294 mg/dl), compared to the reference group. A multiple-adjusted restricted cubic spline model showed a non-linear trend of the significant association between high maternal TC and No-CU (p for linear trend = 0.05, p for quadratic trend <0.05).
High maternal TC at mid-pregnancy was associated with No-CU among SGA infants. Such infants should be carefully followed up to introduce appropriate growth hormonal treatment. The findings may support previous animal experimental studies which indicated that maternal high-fat diet exposure induces impairment of growth and skeletal muscle development in the offspring. Future studies are required to elucidate the detailed mechanism.
未出现追赶生长（No-CU）的足月小样儿（SGA）婴儿存在发生智力和发育障碍的高风险。然而，导致 SGA 婴儿出现 No-CU 的因素尚不清楚。本研究旨在探讨中孕期母体总胆固醇（TC）与足月 SGA 婴儿 3 岁时 No-CU 之间的关系。
日本环境与儿童健康研究（JECS）是一项全国性的前瞻性出生队列研究。我们从总共包含 104062 个胎儿记录的原始 JECS 队列中，共提取了 2222 名母亲和足月 SGA 婴儿（身长和/或体重<-2 个标准差[SD]）的资料，这些婴儿没有先天性异常。根据整个队列中母体 TC 的分布，将参与者按每 5%的五分位数分组，第 20-79 百分位数（204-260mg/dl）为参考组。根据日本儿童生长标准图表，将 3 岁时身高 Z 评分<-2SD 定义为 No-CU。使用多重插补进行多变量调整后的逻辑回归模型。此外，在完整数据集上进行了多调整限制立方样条模型。
共有 362 名（16.3%）儿童在 3 岁时未出现追赶生长。在调整了出生体重 Z 评分、母亲年龄、吸烟状况、孕期体重增加、2 岁时母乳喂养和用餐频率以及父母身高后，与参考组相比，母体 TC 水平处于最高组（≥294mg/dl）的儿童，出现 No-CU 的比值比（95%置信区间）为 2.95（1.28-6.80）。多调整限制立方样条模型显示，母体 TC 水平与 No-CU 之间存在显著的非线性趋势（线性趋势 p 值=0.05，二次趋势 p 值<0.05）。
中孕期母体 TC 水平较高与 SGA 婴儿的 No-CU 有关。此类婴儿应密切随访，以引入适当的生长激素治疗。这些发现可能支持之前的动物实验研究，该研究表明母体高脂肪饮食暴露会导致后代生长和骨骼肌肉发育受损。需要进一步的研究来阐明其详细的机制。
