A retrospective study of pregnancy outcomes when intravenous immunoglobulin is used for the treatment of recurrent spontaneous miscarriages with subchorionic hematoma
Authors: Zhu Liqiong , Huang Yueting , Li Feiyan , Ji Xiaohui , Liu Yukun , Fu Shuai , Zhang Shuning , Deng Kewen , Mo Hanjie , Tan Jianping , Zhang Jianping , Chen Hui 
Published: December 2022

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.