Gestational weight gain in relation to offspring obesity over the life course: a systematic review and bias‐adjusted meta‐analysis

Gestational weight gain (GWG) is considered one of the risk factors for future obesity in the offspring. However, the direction and strength of this association at different periods of offspring life is relatively unknown. This study investigates whether excess or inadequate maternal GWG during pregnancy influences the risk of offspring obesity at different stages in life. A systematic review of published articles was undertaken after a comprehensive search of different databases, and extracted data were meta‐analysed. To quantify offspring obesity estimates in relation to GWG, we stratified obesity estimates within three life stages of the offspring age: <5 years, 5 to <18 years and 18+ years. Our meta‐analysis showed that, compared with offspring of women with adequate GWG, offspring of women who gained inadequate gestational weight were at a decreased risk of obesity (relative risk [RR]: 0.86; 95% confidence interval [CI]: 0.78–0.94), and offspring of women who gained excess weight were at an increased risk of obesity (RR: 1.40; 95% CI: 1.23–1.59). These relationships were similar after stratification by life stage. Findings of this study therefore suggest that excess GWG does influence offspring obesity over the short‐ and long‐term, and should therefore be avoided.     

Copy number variants in patients with short stature

Height is a highly heritable and classic polygenic trait. Recent genome-wide association studies (GWAS) have revealed that at least 180 genetic variants influence adult height. However, these variants explain only about 10% of the phenotypic variation in height. Genetic analysis of short individuals can lead to the discovery of novel rare gene defects with a large effect on growth. In an effort to identify novel genes associated with short stature, genome-wide analysis for copy number variants (CNVs), using single-nucleotide polymorphism arrays, in 162 patients (149 families) with short stature was performed. Segregation analysis was performed if possible, and genes in CNVs were compared with information from GWAS, gene expression in rodents'' growth plates and published information. CNVs were detected in 40 families. In six families, a known cause of short stature was found (SHOX deletion or duplication, IGF1R deletion), in two combined with a de novo potentially pathogenic CNV. Thirty-three families had one or more potentially pathogenic CNVs (n=40). In 24 of these families, segregation analysis could be performed, identifying three de novo CNVs and nine CNVs segregating with short stature. Four were located near loci associated with height in GWAS (ADAMTS17, TULP4, PRKG2/BMP3 and PAPPA). Besides six CNVs known to be causative for short stature, 40 CNVs with possible pathogenicity were identified. Segregation studies and bioinformatics analysis suggested various potential candidate genes.     

Gestational exposure to low‐dose zearalenone disrupting offspring spermatogenesis might be through epigenetic modifications

Zearalenone (ZEA), a F‐2 mycotoxin produced by Fusarium, has been found to be an endocrine disruptor through oestrogen receptor signalling pathway to impair spermatogenesis. The disruption on reproductive systems by ZEA exposure might be transgenerational. In our previous report, we have found that low dose (lower than no‐observed effect level, NOEL) of ZEA impaired mouse spermatogenesis and decreased mouse semen quality. The purpose of the current investigation was to explore the impacts of low‐dose ZEA on spermatogenesis in the offspring after prenatal exposure and the underlying mechanisms. And it demonstrated that prenatal low‐dose ZEA exposure disrupted the meiosis process to inhibit the spermatogenesis in offspring and even to diminish the semen quality by the decrease in spermatozoa motility and concentration. The DNA methylation marker 5hmC was decreased, the histone methylation markers H3K9 and H3K27 were elevated, and oestrogen receptor alpha was reduced in the offspring testis after prenatal low‐dose ZEA exposure. The data suggest that the disruption in spermatogenesis by prenatal low‐dose ZEA exposure may be through the modifications on epigenetic pathways (DNA methylation and histone methylation) and the interactions with oestrogen receptor signalling pathway. Moreover, in the current study, the male offspring were indirectly exposed to low‐dose ZEA through placenta and the spermatogenesis in offspring was disrupted which suggested that the toxicity of ZEA on reproductive systems was very severe. Therefore, we strongly recommend that greater attention should be paid to this mycotoxin to minimize its adverse impact on human spermatogenesis.     

肠道菌群结构改变与妊娠期糖尿病的关系研究

背景　妊娠期糖尿病（GDM）在近年妊娠期疾病中所占比例日益增加,其高发病率为我国母婴健康和公共卫生事业带来了巨大危害。目前研究提示人类肠道菌群的结构改变与相关代谢性疾病密切相关,越来越多的证据提示肠道菌群结构和相对比例的改变可能是糖尿病、肥胖等疾病的高危因素。目的　探究肠道球形梭菌和多形拟杆菌水平改变与GDM发生之间的关系。方法　本研究为巢式病例对照研究。选取2018-03-01至2019-03-30于新疆医科大学第一附属医院就诊的1 034例妊娠妇女,在其首次就诊于本院并确认妊娠时纳入观察队列,之后每4周返回医院行随访并完成产检,当确诊GDM时为最后一次随访。将确诊为GDM的受试者作为病例组,依据病例组受试者年龄、孕周、时间等相关信息进行1∶1匹配对照组受试者。比较对照组和病例组一般资料,入组时、妊娠20周、诊断GDM时球形梭菌、多 形拟杆菌水平。分析病例组不同时间点球形梭菌及多形拟杆菌与空腹血糖间的相关性。结果　1 034例观察队列中,28例受试者中途退出,5例受试者失访,故共计1 001例受试者完成随访,其中90例（8.99％）被诊断为GDM,即病例组。对照组与病例组年龄、受教育程度、糖尿病家族史发生率、腹围、多囊卵巢综合征发生率、高血压发生率比较,差异无统计学意义（P>0.05）。两组入组时球形梭菌、多形拟杆菌水平比较,差异无统计学意义（P>0.05）;病例组妊娠20周、诊断GDM时球形梭菌、多形拟杆菌水平高于对照组（P<0.05）。病例组妊娠20周、诊断GDM时球形梭菌、多形拟杆菌水平高于入组时（P<0.05）;对照组在病例组诊断GDM对应的时间点的多形拟杆菌水平高于入组时和妊娠20周时（P<0.05）。病例组诊断GDM时球形梭菌、多形拟杆菌与诊断GDM时空腹血糖呈正相关（r值分别为0.435、0.342,P值分别为<0.001、0.001）。结论　球形梭菌与多形拟杆菌的结构改变可能是导致GDM发病的原因之一。     

小于胎龄儿0~24月龄体格生长状况分析

背景　出生后2年是小于胎龄儿（SGA）完成追赶生长的关键时期,其生长与适于胎龄儿（AGA）相比具有特殊性,但目前尚缺乏对于早期SGA随访的指南,对于早期SGA生长特点还需进一步研究。目的　探讨SGA出生后2年内的体格生长规律。方法　采用前瞻性队列研究方法,选取出生于2016年3月-2017年3月且出生后2年内定期在厦门市妇幼保健院儿童保健科体检的SGA,以及同期出生的足月AGA作为研究对象,根据2015年中国不同胎龄新生儿出生体质量曲线,结合胎龄和出生体质量分为足月SGA组（n=147）、早产SGA组（n=42）、足月AGA组（n=164）,分别在出生时、3月龄（±7 d）、6月龄（±7 d）、12月龄（±14 d）、18月龄（±14 d）、24月龄（±14 d）测量其体质量、身长、头围,经Z值转换后分析其生长水平及生长速度。结果　重复测量方差分析结果显示,组间、时间对年龄别体质量Z值（WAZ）、年龄别身长Z值（LAZ）、年龄别体质指数（BMI）Z值（BMIZ）、年龄别头围Z值（HCZ）存在交互作用,且主效应显著（P<0.05）;简单效应分析显示,3组间WAZ、LAZ、BMIZ、HCZ比较,差异均有统计学意义（P<0.05）;3组各时间点WAZ、LAZ、BMIZ比较,差异均有统计学意义（P<0.05）。足月SGA组和早产SGA组3月龄、6月龄、12月龄、18月龄、24月龄WAZ、LAZ、HCZ小于足月AGA组,足月SGA组3月龄、6月龄、12月龄、18月龄、24月龄BMIZ小于足月AGA组,早产SGA组3月龄、6月龄BMIZ小于足月AGA组（P<0.05）。3组间0~3月龄、>3~6月龄、>6~12月龄?WAZ,>3~6月龄、>6~12月龄?LAZ,0~3月龄、>6~12月龄?BMIZ,>3~6月龄?HCZ比较,差异均有统计学意义（P<0.05）。足月SGA组和早产SGA组0~3月龄?WAZ高于足月AGA组,足月SGA组>3~6月龄?WAZ高于足月AGA组,足月SGA组>3~6月龄、>6~12月龄?LAZ高于足月AGA组,足月SGA组和早产SGA组0~3月龄、>6~12月龄?BMIZ高于足月AGA组,早产SGA组0~3月龄?BMIZ高于足月SGA组,足月SGA组和早产SGA组0~3月龄?HCZ高于足月AGA组（P<0.05）。3组间3月龄、6月龄、12月龄、18月龄、24月龄体质量追赶生长率比较,差异均有统计学意义（P<0.05）;其中,足月SGA组和早产SGA组3月龄、6月龄、12月龄、18月龄、24月龄体质量追赶生长率大于足月AGA组（P<0.017）。3组间6月龄、12月龄、18月龄、24月龄身长量追赶生长率比较,差异均有统计学意义（P<0.05）;其中,足月SGA组和早产SGA组12月龄、18月龄、24月龄身长追赶生长率大于足月AGA组（P<0.017）。结论　出生后1年SGA体质量、身长加速生长。0~3月龄以体质量追赶为主,身长发生追赶时间落后于体质量,头围追赶主要在出生后6月龄内。而早产SGA的BMI在早期增长更加快速。     

妊娠期糖尿病伴牙周炎治疗研究进展

牙周炎和妊娠期糖尿病（gestational diabetes mellitus,GDM）都是十分常见的慢性病。研究发现,GDM与牙周炎之间可能存在相关性,GDM影响牙周炎发展的严重程度,牙周炎对GDM的发展亦有着推动作用。GDM伴牙周炎的发病机制复杂,可能对正常妊娠及胎儿生长发育产生不良影响,因此,对GDM伴牙周炎患者的综合治疗需持谨慎的态度。迄今为止,对于GDM合并牙周炎的治疗尚存在争议,主要以降血糖、降低炎症反应的治疗为主,但并无统一的治疗方案。文章回顾了近年来国内外相关研究,就GDM伴牙周炎患者的治疗研究进展做一综述,为其临床诊疗及科学研究提供新的思路。