A retrospective study of pregnancy outcomes when intravenous immunoglobulin is used for the treatment of recurrent spontaneous miscarriages with subchorionic hematoma

Li-qiong Zhu, Yue-ting Huang, Fei Li, Xiaohui Ji, Yu-kun Liu, S. Fu, Shuning Zhang, Kewen Deng, Hanjie Mo, Jian-ping Tan, Jianping Zhang, Hui Chen
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Abstract

Objective: To investigate the incidence of subchorionic hematoma (SCH), pregnancy outcomes and health status of offspring in patients with recurrent spontaneous miscarriage (RSA) treated with intravenous immunoglobulin (IVIg). Methods: The records of 775 patients with RSA were retrospectively reviewed. RSA with SCH were all treated with IVIg. Pregnancy outcomes examined were the rates of miscarriage, stillbirth, pre-term birth, and live birth. The pregnancy complications and comorbidities examined included oligohydramnios, hypertensive disorders, gestational diabetes, premature membrane rupture, placental adhesions, placenta previa, postpartum hemorrhage, placental abruption, and low birth weight. The health status of offspring of RSA patients with SCH was followed up by telephone, record physical and neurodevelopmental performance, and diseases under 5 years old, then compare with common children. Based on the ratio of SCH volume to that of the gestational sac, SCH was divided into small (ratio < 20%), moderate (ratio = 20%–50%), and large (ratio > 50%). Statistical analysis was performed with IBM SPSS Statistics 23.0. Comparison of continuous variables was analyzed using t-test. Categorical variables were compared by using χ2 test or Fisher’s exact test. Multivariable logistic regression was used for adjusting certain confounders. Results: Of the 775 patients with RSA, 110 RSA had a SCH (incidence = 14.2%). SCH was firstly found at 8.29 (5.00–11.58) weeks pregnant. There was no statistical difference in age, number of pregnancies, parity and miscarriages between patients with and without an SCH. The incidence of SCH in in-vitro fertilization embryo transfer (IVF-ET) patients was higher than in natural pregnancy patients (27.9% vs. 13.1%, P < 0.05). RSA with SCH patients with pregnancy outcome data called Group A (n = 94), RSA without SCH patients with pregnancy outcome data called Group B (n = 556), the rates of miscarriage (17.0% vs.12.4%), stillbirth (0 vs. 0.4%), pre-term delivery (9.6% vs. 10.8%), live birth (84.7% vs. 80.9%), and pregnancy complications were not different between Group A and B. The rate of vaginal bleeding in the Group A was higher than in the Group B (P < 0.05). There was no significant difference in the birth weight, the rate of low birth weight infants, neonatal asphyxia, or neonatal pneumonia between the groups. 43 puerpera in the experimental group were willing to receive telephone follow-up, who gave birth from December 2015 to November 2016. A total of 43 live births were delivered. By March 2022, the children were 5 years and 4 months old to 6 years and 3 months old. There is no difference in the physical development compared with common children. A child was diagnosed with neuropsychological delay. The incidence rate of community acquired pneumonia (CAP) was 27.9 per 1000 person-years for children under 5 years. In patients with a SCH and vaginal bleeding, the rate of preterm birth was 16.7%. The rate of preterm birth was highest (36.4%) in RSA patients with a large SCH, and only 5.7% in patients with a small SCH (P < 0.05). Patients treated with IVIg had mild adverse reactions such as hypothermia, dizziness, and rash with rates of 1.8%, 1.8%, and 0.9%, respectively. Conclusion: The incidence of SCH was 14.2% in RSA. Pregnancy outcomes were similar between the RSA patients with a SCH treated with IVIg treatment and RSA patients without a SCH. There is no difference in the physical development between offspring of RSA with SCH and common children, and effect of SCH on neurodevelopment of offspring needs to be further verified by expanding the sample size. RSA patient with a SCH are prone to have vaginal bleeding and abdominal pain. For RSA patients with a SCH and vaginal bleeding, or SCH volume ratio > 50%, even after IVIg, still leads to a significantly higher preterm birth rate.
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静脉注射免疫球蛋白治疗复发性自然流产合并绒毛膜下血肿的妊娠结局回顾性研究
目的:探讨静脉注射免疫球蛋白(IVIg)治疗复发性自然流产(RSA)患者的绒毛膜下血肿(SCH)发生率、妊娠结局及后代健康状况。方法:回顾性分析775例RSA患者的临床资料。RSA和SCH均用IVIg治疗。妊娠结局包括流产、死产、早产和活产的发生率。检查的妊娠并发症和合并症包括羊水过少、高血压、妊娠糖尿病、胎膜早破、胎盘粘连、前置胎盘、产后出血、胎盘早剥和低出生体重。通过电话随访RSA患儿的子代健康状况,记录5岁以下儿童的身体和神经发育表现及疾病情况,并与普通儿童进行比较。根据SCH体积与妊娠囊体积之比,将SCH分为小(比例< 20%)、中(比例= 20% ~ 50%)和大(比例> 50%)。采用IBM SPSS Statistics 23.0进行统计学分析。连续变量比较采用t检验。分类变量比较采用χ2检验或Fisher精确检验。多变量逻辑回归用于调整某些混杂因素。结果:775例RSA患者中,110例RSA合并SCH(发生率为14.2%)。妊娠8.29(5.00-11.58)周首次发现SCH。发生和未发生SCH的患者在年龄、妊娠次数、胎次、流产等方面均无统计学差异。体外受精胚胎移植(IVF-ET)患者发生SCH的发生率高于自然妊娠患者(27.9% vs. 13.1%, P < 0.05)。有妊娠结局资料的RSA合并SCH患者称为A组(n = 94),无妊娠结局资料的RSA合并SCH患者称为B组(n = 556),流产率(17.0% vs.12.4%)、死胎率(0 vs. 0.4%)、早产率(9.6% vs. 10.8%)、活产率(84.7% vs. 80.9%)、妊娠并发症在A组和B组之间无显著差异。A组阴道出血率高于B组(P < 0.05)。两组在出生体重、低出生体重儿发生率、新生儿窒息或新生儿肺炎方面无显著差异。实验组中愿意接受电话随访的产妇43例,均为2015年12月~ 2016年11月分娩的产妇。共有43名活产婴儿出生。到2022年3月,孩子们的年龄从5岁4个月到6岁3个月。与普通儿童相比,他们的身体发育没有什么不同。一个孩子被诊断为神经心理发育迟缓。5岁以下儿童社区获得性肺炎(CAP)发病率为27.9 / 1000人年。在伴有阴道出血的患者中,早产率为16.7%。大SCH组早产率最高(36.4%),小SCH组早产率仅为5.7% (P < 0.05)。接受IVIg治疗的患者有轻度不良反应,如体温过低、头晕和皮疹,发生率分别为1.8%、1.8%和0.9%。结论:RSA中SCH的发生率为14.2%。经IVIg治疗的RSA伴SCH患者与未伴SCH患者妊娠结局相似,伴SCH的RSA子代与普通子代体格发育无差异,SCH对子代神经发育的影响有待扩大样本量进一步验证。RSA合并SCH的患者容易出现阴道出血和腹痛。对于有SCH合并阴道出血的RSA患者,或SCH容积比为50%的患者,即使在IVIg后,仍会导致明显较高的早产率。
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