Medicine (Baltimore). 2018 Mar;97(9):e0053. doi: 10.1097/MD.0000000000010053.
Motor development delay in offspring is associated with prenatal telbivudine exposure.Zhou C1,2,3, Yu Y1, Yang Q4,3, Wang H4,3, Hou M4,3, Jin L4,3, Zhang F1, Sheng J5, Miao M1, Yang X1, Huang HF1,4,2,3. Author information 1Woman's Hospital, School of Medicine, Zhejiang University.2Key Laboratory of Reproductive Genetics, Ministry of Education.3Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, China.4International Peace Maternal and Child Health Hospital, Shanghai Jiao Tong University.5Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University.
AbstractTelbivudine is an orally nucleoside analog with potent and specific antihepatitis B virus (HBV) activity, and it has been reported to block mother-to-infant transmission. However, few studies have focused on the safety of prenatal exposure for offspring development.This is a prospective noninterventional study. Participants were enrolled during delivery through the Women's Hospital of Zhejiang University School of Medicine between January 2012 and September 2013. Neonate's umbilical cord arterial blood (UCAB) was collected after delivery. Hepatitis B virus DNA copy, HBV serology, alanine aminotransferase (ALT), creatine kinase (CK), creatinine (CRE), and blood urea nitrogen (BUN) were measured. The development of the offspring was evaluated by the Chinese Revision of Bayley Scales of Child Development (BSCD-CR) at 12 to 24 months old.Around 30 and 31 chronic hepatitis B mothers were recruited in untreated group (non-LdT group) and telbivudine-treatment group (LdT group), respectively, and 2 children (one in non-LdT group and 1 in LdT group) were lost in follow-up. Sixty-one normal women and their children were recruited as a normal control (control group). Compared with non-LdT group, telbivudine treatment effectively blocks HBV transmission from mother to infant. However, CK in UCAB was significantly increased in the LdT group. Moreover, children with prenatal telbivudine exposure showed lower level of serum creatinine than non-LdT group, reduction of psychomotor developmental index and increased risk of motor development delay.Prenatal telbivudine exposure is correlated with motor development delay in offspring.
"The Chinese Revision of the Bayley Scales of Child Development (BSCD-CR) was used to evaluate motor and mental development. The test is a revision of Bayley Scales of Child Development-Second Edition (BSCD-II) and provides 2 subscales, a motor scale providing a psychomotor developmental index (PDI) and a mental scale yielding a mental developmental index (MDI). The mean score (± standard deviation) for both indexes for a normal population is 100 ± 15, and a score of less than 85 indicates developmental delay.[16]
中国修订的贝利儿童发展量表（BSCD-CR）被用于评估运动和智力发育。 该测试是对贝利儿童发育量表第二版（BSCD-II）的修订，并提供2个分量表，一个提供心理运动发育指数（PDI）的运动量表和一个产生心智发育指数（MDI）的心理量表。 正常人群的两项指标的平均得分（±标准差）为100±15，小于85的得分表示发育迟缓[16]。"
Our results showed that prenatal LdT exposure group showed increased CK in fetal UCAB, reduced serum Cre, PDI score and thus appears to increase the risk of delayed motor development.
我们的结果显示，产前LdT暴露组显示胎儿UCAB中CK增加，血清Cre，PDI评分降低，因此似乎增加了延迟运动发育的风险。
There are limitations in the present study. Some parental information was not obtained, such as social class, income and smoking history, which could be confounding factors in this study. In addition, children in 12 to 24 months old were in the rapid development stage and the follow-up period was too short to document long-term motor development disorders. As mentioned above, long-term follow-up with more samples is necessary to validate our findings.
目前的研究存在局限性。 没有获得一些父母的信息，如社会阶层，收入和吸烟史，这可能是本研究中混杂因素。 此外，12至24个月大的儿童处于快速发展阶段，随访时间太短，无法记录长期运动发育障碍。 如上所述，需要更多样本的长期随访来验证我们的发现。
Intrauterine transmission of HBV is considered to be the most important reason for the failure of passive-active immunoprophylaxis in preventing MTCT [7,9]. Different diagnostic criteria [12–20] had been applied for the diagnosis of HBV intrauterine infection. Since there is no consensus on the diagnosis criteria of HBV intrauterine infection, different proofs that could identify the existence of HBV components in serum of newborns had been used (Table 1). The exact mechanism of intrauterine transmission of HBV remains to be illuminated. The most frequently mentioned hypotheses involve: (a) serum/body fluid transmission, which usually occurs in conditions of placenta damage caused by contraction of the uterine muscle such as threatened abortion [21], invasive procedures into the uterus like amniocentesis during pregnancy [22] or specific infections like TORCH (Toxoplasma, Rubella, Cytomegalovirus and Herpes Simplex) infection; (b) cellular transmission, which refers to transmission of HBV from the maternal side to the fetal side through placenta cells and transfer of infected peripheral blood mononuclear cell (PBMC) [15] from the maternal circulation system into the fetal circulation system; and (c) genetic transmission, germ cells like sperm and oocytes could be infected by HBV and transferred the virus to the embryo [23,24].
2.1。宫内传播
Accumulated proofs have identified that high serum HBV DNA levels and HBeAg positive status in pregnant mothers are key factors for indicating the increased risk of MTCT of HBV, especially in intrauterine transmission of HBV through villous capillary endothelial cells [25–27]. Wiseman et al. [28] have shown a transmission rate of 9% for newborns born from mothers with virus load > 8 log10 copies/ml (7.3 log10 IU/ml) despite standard passive-active immunoprophylaxis administration and no transmission below this cut-off. Recent studies even proposed a lower level of 6 log10 copies/ml (5.3 log10 IU/ml) of maternal viremia as the cut-off [29,30] and the reported rate [15,31] of MTCT of HBV to newborns ranged from 8% to nearly 30% if maternal HBV DNA levels are higher than 6 log10 copies/ml (5.3 log10 IU/ml).
已有证据表明孕妇高血清HBV DNA水平和HBeAg阳性状态是指示HBV MTCT风险增加的关键因素，尤其是通过绒毛毛细血管内皮细胞发生HBV的宫内传播[25-27]。 Wiseman等人 [28]尽管采用标准的被动主动免疫预防给药，但病毒载量> 8log10拷贝/ ml（7.3log10IU / ml）的母亲新生儿的传播率为9％，并且在该截止值以下没有传播。 最近的研究甚至提出较低的6 log10拷贝/ ml（5.3 log10 IU / ml）为HBV的MTCT对新生儿的截止[29,30]. 如果母亲HBV DNA水平高于6log10拷贝/ ml（5.3log10IU / ml），HBV MTCT报告给新生儿的比例[15,31]介于8％至近30％. 作者: brad2309 时间: 2018-3-3 15:53
