173例轻度和中度胎儿侧脑室扩张的妊娠结局和神经系统发育随访

Pregnancy outcomes and neurodevelopment in 173 cases of mild or moderate fetal ventriculomegaly

目的探讨不同程度、类型和宫内转归的胎儿侧脑室扩张的妊娠结局和神经系统发育情况。方法采用队列研究设计，分析2010年3月至2016年6月因产前超声提示＂胎儿侧脑室扩张＂到南方医科大学南方医院妇产科产前诊断中心就诊的173例单胎妊娠孕妇的临床资料。选取同期在本院产前检查的30例正常孕妇作为对照组。对继续妊娠者随访婴儿至生后6月龄，胎儿侧脑室宽度≥10 mm且≤12 mm为轻度侧脑室扩张（轻度组），〉12 mm且〈15 mm为中度侧脑室扩张（中度组）。当侧脑室扩张不伴其他颅内外异常、羊水量异常或超声软指标异常时为孤立性侧脑室扩张（isolated ventriculomegaly，IVM），否则为非孤立性侧脑室扩张（non-isolated ventriculomegaly，NIVM）。173例单胎妊娠孕妇中轻度组107例，其中IVM 54例，NIVM 53例；中度组66例，其中IVM 26例，NIVM 40例。所有研究对象均除外了染色体异常。采用新生儿行为神经测定（neonatal behavioral neurological assessment，NBNA）方法对生后7 d的新生儿进行神经发育情况评估，采用贝利婴幼儿发展量表的智力发育指数（mental development index，MDI）和心理运动发育指数（psychomotor development index，PDI）对6月龄婴幼儿进行神经系统发育情况评估。统计学方法采用t检验、χ2检验（或Fisher精确概率法）、非参数检验、Mann-Whitney检验、Kruskal-Wallis H检验。 结果（1）脑室扩张消退、稳定、进展：轻度组分别为78例（72.9%）、25例（23.4%）和4例（3.7%），中度组分别为30例（45.4%）、25例（37.9%）和11例（16.7%）（χ2=15.769，P〈0.001）；轻度组内IVM亚组和NIVM亚组之间比较，差异无统计学意义（χ2=2.412，P=0.299）；中度组内IVM亚组分别为17例（65.4%）、8例（30.8%）和1例（3.8%），NIVM组分别为13例（32.5%）、17例（42.5%）和10例（25.0%）（χ2=8.552，P=0.014）。（2）164例孕妇继续妊娠并顺利分娩。新生儿生后7 d NBNA评分比较，侧脑室扩张组低于对照组[（37.70±1.80）与（38.53±1.38）分，t=－2.424，P〈0.05]。轻度组NBNA评分〈36分、≥36分者分别为5例（4.7%）和101例（95.3%），中度组分别为8例（13.8%）和50例（86.2%）（χ2=4.231，P=0.004）；轻度组和中度组内IVM和NIVM亚组NBNA评分比较，差异均无统计学意义（χ2值分别为0.210和0.201，P值均〉0.05）。（3）侧脑室扩张组胎儿生后6个月失访27例，共137例进行神经系统发育评估。侧脑室扩张组PDI评分低于对照组比较[（90.50±10.85）与（95.80±9.65）分，t=－2.471，P=0.014]，但MDI评分比较差异无统计学意义[（95.42±11.20）与（99.50±12.00）分，t=－1.786，P=0.076]。（4）PDI评分优秀、中等、低下者构成比：轻度组与中度组、轻度组内IVM与NIVM亚组比较，差异均无统计学意义（Z值分别为－1.869和－1.946，P值分别为0.062和0.052）；中度组内IVM和NIVM亚组间比较，差异有统计学意义[3例（15.0%）、16例（80.0%）和1例（5.0%）与1例（3.1%）、24例（75.0%）和7例（21.9%），Z=－2.097，P=0.036]；宫内转归消退、稳定和进展组比较，差异亦有统计学意义[9例（10.6%）、75例（88.2%）和1例（1.2%）；3例（6.5%）、37例（80.4%）和6例（13.1%）；0、2例（2/6）和4例（4/6）；χ2=19.808，P〈0.001]。（5）MDI评分优秀、中等、低下者构成比：轻度组和中度组、轻度组和中度组组内IVM和NIVM亚组比较，差异均无统计学意义（Z值分别为－0.826、－1.457和0.720，P值分别为0.409、0.145和0.472）；宫内转归消退、稳定和进展组比较，差异均有统计学意义[13例（15.3%）、71例（83.5%）、1例（1.2%）；2例（4.4%）、41例（89.1%）、3例（6.5%）；0、5例（5/6）、1例（1/6）；χ2=7.980，P=0.018]。结论侧脑室扩张是否合并异常及其宫内转归为影响其预后的主要因素，轻度侧脑室扩张胎儿亦有神经系统发育不良的风险，应引起重视并注意生后定期随访。

ObjectiveTo investigate pregnancy outcomes and neurodevelopment in fetuses with ventriculomegaly.MethodsThis was a cohort study of 173 gravidas with singleton pregnancy who were diagnosed with fetal ventriculomegaly by ultrasound in Prenatal Diagnostic Center of Nanfang Hospital Affiliated to Southern Medical University from March 2010 to July 2016. Thirty normal gravidas who received antenatal care in the same hospital and at the same period were selected as control. Clinical data were collected. Gravidas who had chosen to continue their pregnancy were followed up to monitor the variations of fetal ventricular. Fetal mild and moderate ventriculomegaly were respectively defined as a ventricular atrial width of 10-12 mm and 〉12 mm but 〈15 mm. Isolated ventriculomegaly （IVM） indicated those without any other ultrasound abnormalities, otherwise the case would be defined as non-isolated ventriculomegaly （NIVM）. Among the 173 gravidas, 54 cases were mild IVM, 53 mild NIVM, 26 moderate IVM and 40 moderate NIVM. Fetuses with chromosome abnormalities were excluded from the study. Neonatal behavioral neurological assessment （NBNA） was used to analyze the neonatal neurodevelopment at the age of 7 days, and Bayley scales of infant development was used to evaluate the development of nervous system at the age of 6 months through analyzing their mental development index （MDI） and psychomotor development index （PDI）. Statistical methods included t test, χ2 test （or Fisher＇s exact test）, nonparametric test, Mann-Whitney test and multiple Kruskal-Wallis H test.Results（1） Among the 107 fetuses with mild ventriculomegaly, 72.9% （78）, 23.4% （25） and 3.7% （4） of them regressed, stabilized and progressed,respectively; however, among the 66 moderate cases, the figures were 45.4% （30）, 37.9% （25） and 16.7% （11） respectively （χ2=15.769, P〈0.001）. For those in the IVM and NIVM subgroups within the moderate ventriculomegaly group, significant difference was shown [17（65.4%）, 8（30.8%） and 1（3.8%） vs 13（32.5%）, 17（42.5%） and 10（25.0%）, χ2=8.552, P=0.014], but not within the mild groups （χ2=2.412, P=0.299）. （2） There were 164 gravidas who continued their pregnancy and delivered. Significant differences in NBNA score were observed between the ventriculomegaly group and the control （37.70±1.80 vs 38.53±1.38, t=-2.424, P〈0.05）. Numbers of neonates with NBNA score〈36 and ≥36 points were 5（4.7%） and 101（95.3%） in the mild group, and 8（13.8%） and 50（86.2%） in the moderate group （χ2=4.231, P=0.004）. There was significant difference in NBNA score between the IVM and NIVM subgroup within neither mild nor moderate group （χ2 were 0.210 and 0.201, P were 1.000 and 0.720）. （3） Totally, 137 cases completed the assessment of nervous system development at the age of 6 months. There was significant difference in PDI score between the ventriculomegaly group and the control （90.50±10.85 vs 95.80±9.65, t=-2.471, P=0.014）, but not in MDI score （95.42＋11.20 vs 99.50＋12.00, t=-1.786, P=0.076）. （4） The comparison of the proportion of excellent, average and poor PDI scores： Significant differences were found between the IVM and NIVM subgroup within the moderate ventriculamegaly group and in the different intrauterine outcome groups [IVM vs NIVM groups： 3（15.0%）, 16（80.0%） and 1（5.0%） vs 1（3.1%）, 24（75.0%） and 7（21.9%）, Z=-2.097, P=0.036; intrauterine regression, stable and progress group： 9（10.6%）, 75（88.2%） and 1（1.2%）; 3（6.5%）, 37（80.4%） and 6（13.1%） vs 0, 2（2/6） and 4（4/6）, χ2=19.808, P〈0.001], but not between the mild and moderate vetriculamegaly group, or between the subgroups within the mild ones （Z were -1.869 and -1.946, P were 0.062 and 0.052）. （5） The comparison of the proportion of excellent, average and poor scores of MDI： Significant difference was only found among the different intrauterine outcome groups[13（15.3%）, 71（83.5%）, 1（1.2%）; 2（4.4%）, 41（89.1%）, 3（6.5%） vs 0, 5（5/6）, 1（1/6）; χ2=7.980, P=0.018], but not in any other comparisons （all P〉0.05）.ConclusionsPrognosis of fetal ventriculomegaly is affected by co-existed abnormalities and intrauterine progression. Fetus with mild ventriculomegaly can also have risk of abnormal neural development, suggesting that we should pay much attention to such cases and a regular follow-up is required.