Pregnancy Outcomes of Non-Visualization of The Foetal Gallbladder From A Chinese Tertiary Single Centre And Literature Review

Objection To explore the clinical features and prognosis of non-visualization of fetal gallbladder (NVFGB). Methods 65 cases diagnosed of NVFGB in the Peking University First Hospital was collected retrospectively from January, 2019 to December, 2020. Results 49 cases were successfully followed up. Among them, the gallbladder of 21 fetuses (42.9%) was visible later, either in the later pregnancy or after birth. In the rest 28 cases (57.1%), the gallbladders were not seen during the whole pregnancy. 11 of 28 fetuses (39.3%) with NVFGB were complicated with other structure anomaly. In the remaining 17 cases of isolated NVFGB (60.7%), one case was diagnosed of congenital biliary atresia, 3 cases of small gallbladder, 1 case of gallstone and one case of irregular size of gallbladder. There are 9 cases who underwent prenatal diagnosis, with 4 cases of abnormal result. Conclusion Prenatal ultrasound plays a role in the early recognize of abnormal gallbladder, which will improve the postnatal prognosis.

Non-Invasive Prenatal Detecting of Achondroplasia In Earlier Stage of Pregnancy By Droplet-Digital PCR

Background: Achondroplasia (ACH) is generally detected by abnormal prenatal ultrasound findings in the late stage of pregnancy and then confirmed by molecular genetic testing of fetal genomic DNA obtained invasively. Most ACH cases appear to be de novo mutations with FGFR3 gene, so it is a challenge to screen ACH fetus out in the early stage of pregnancy.Objective: The aim of this study was to validate the possibility of detect fetus ACH along with non-invasive prenatal screening(NIPS) routinely in the early stage of pregnancy.Methods: 5927 cases of pregnant women undergoing NIPS were enrolled in this study. An additional 5ml of blood was collected together with NIPS blood sampling. Cell free DNA was extracted for the detecting of fetus ACH. Droplet-digital PCR(ddPCR) method based on the amplification of the two possible mutant alleles (c. 1138G>A and c. 1138G>C) of FGFR3 gene was performed to screen fetus ACH. Prenatal ultrasound and amniocentesis were then performed to confirm the positive screening result of ACH cases. The mutation sites of fetus were identified via Sanger sequencing by using amniotic fluid cells. For the screen negative cases of pregnant women, we followed up the results of prenatal diagnosis or the general conditions of the newborns.Results: One pregnant woman with fetus ACH were screened out at 22 weeks by Non-invasive prenatal detecting. Later prenatal ultrasound confirmed fetal skeletal dysplasia. Sanger sequencing confirmed de novo FGFR3 1138G>A mutant of the fetus. No ACH fetus or newborns were found in the rest detected negative cases of enrolled pregnant women.Conclusion: ddPCR technology could effectively identify de novo mutation like ACH of fetus noninvasively. We prospect the clinical application of ddPCR can expand the range of prenatal screen in the future.

Diagnostic Value of Prenatal Ultrasound Parameters and Esophageal Signs in Pouch and Lower Thoracic Segment in Fetuses with Esophageal Atresia

In order to investigate the diagnostic value of prenatal ultrasound parameters and signs of pouch and lower thoracic esophagus in the fetus with esophageal atresia (EA), the prenatal ultrasound data of 35 EA fetuses (observation group) confirmed by autopsy after induced labor or postnatal surgery and imaging examination in our hospital from May 2019 to May 2021 were retrospectively analyzed and compared with 35 normal postnatal fetuses (control group). General information and prenatal ultrasound parameters of the two groups, including head circumference (HC), abdominal circumference (AC), double parietal diameter (BPD), fetal body weight (EFW), and signs (small or unmanifested gastric vesicles, amniotic fluid, neck or upper chest pouch, lower chest esophagus not visible), were analyzed using logistic regression. The logistic multifactor regression model for EA diagnosis was established, and the diagnostic value for EA was analyzed. As a result, the HC, AC, and EFW of the observation group were lower than those of the control group, the gastric bubbles were small or not displayed, the amniotic fluid was more, and the signs of neck or upper chest pouch and lower chest esophagus were not visible in the observation group ( P < 0.05 ). Logistic regression analysis showed that decreased ultrasound parameters HC, AC, EFW, small or no gastric bubble, amniotic fluid, neck or upper chest pouch, and no visible signs of lower chest esophagus were all risk factors for EA ( P < 0.05 ). And in the prenatal ultrasound diagnostic model of EA was established, logistic P = − 19.851 + HC × 0.384 + AC × 0.682 + EFW × 0.695 + small or no gastric vesicle × 3.747 + amniotic fluid × 3.607 + cervical or upper chest sac × 4.104 + invisible lower thoracic esophagus × 4.623 .When logistic P > 0.468 , AUC was 0.891, χ 2 was 7.764, diagnostic sensitivity was 91.24%, and specificity was 79.22%. To draw a conclusion, prenatal ultrasound parameters and signs are of great value in the diagnosis of EA. Independent influencing factors of EA include small or no HC, AC, EFW and gastric vesicles, polyhydramnios, neck or upper chest pouch, and invisible lower thoracic esophagus. Logistic multifactor regression model has a high coincidence rate for the prenatal diagnosis of EA, providing a basis for clinical decision-making.

Prenatal Diagnosis of 17p11.2 Copy Number Abnormalities Associated With Smith–Magenis and Potocki–Lupski Syndromes in Fetuses

Smith-Magenis syndrome and Potocki-Lupski syndrome are rare autosomal dominant diseases. Although clinical phenotypes of adults and children have been reported, fetal ultrasonic phenotypes are rarely reported. A retrospective analysis of 6,200 pregnant women who received invasive prenatal diagnosis at Fujian Provincial Maternal and Child Health Hospital between October 2016 and January 2021 was performed. Amniotic fluid or umbilical cord blood was extracted for karyotyping and single nucleotide polymorphism array analysis. Single nucleotide polymorphism array analysis revealed six fetuses with copy number variant changes in the 17p11.2 region. Among them, one had a copy number variant microdeletion in the 17p11.2 region, which was pathogenically analyzed and diagnosed as Smith-Magenis syndrome. Five fetuses had copy number variant microduplications in the 17p11.2 region, which were pathogenically analyzed and diagnosed as Potocki-Lupski syndrome. The prenatal ultrasound phenotypes of the six fetuses were varied. The parents of two fetuses with Potocki-Lupski syndrome refused verification. Smith-Magenis syndrome in one fetus and Potocki-Lupski in another were confirmed as de novo. Potocki-Lupski syndrome in two fetuses was confirmed to be from maternal inheritance. The prenatal ultrasound phenotypes of Smith-Magenis syndrome and Potocki-Lupski syndrome in fetuses vary; single nucleotide polymorphism array analysis is a powerful diagnostic tool for these diseases. The ultrasonic phenotypes of these cases may enrich the clinical database.

Epidemiological Aspects, Prenatal Screening and Diagnosis of Congenital Heart Defects in Beijing

Background: In China, congenital heart disease (CHD) is the most common birth defect type, with approximately 13,000 new cases annually. This study aimed to investigate high-risk factors, prenatal screening and prenatal diagnosis as a basis for clinical decisions.Methods: All CHD cases identified from 2018 to 2020 were obtained from the Beijing city birth defect surveillance system and prenatal diagnosis institutions. The prenatal CHD diagnosis was confirmed by fetal echocardiography and amniotic fluid or cord blood genetic examination. Chi-square, odds ratio (OR), 95% confidence interval (CI), and univariate and multivariate logistic analyses were used to explore the high-risk factors, prenatal screening and prenatal diagnosis of CHD. Results: In total, 6,786/594,860 fetuses with CHD were diagnosed by prenatal echocardiography. The average incidence of CHD was 11.4 per 1,000 births, with an increase of 30.7 per 1,000 births from 2018 to 2020 (P &lt; 0.05); the average incidence of complex CHD (CCHD) was 2.02 per 1,000 births, with no significant change from 2018 to 2020 (P &gt; 0.05). Women age ≥35 years (OR 1.06, 95% CI 0.77–1.46) was at higher risk of having babies with CHD than women aged 21–34 years. Overall, CHD incidence increased with maternal age (OR1.03, 95% CI 1.02–1.03). Additionally, women who had a non-local household registration (OR 1.16, 95% CI 1.10–1.22) or had diabetes mellitus (DM) (OR 1.16, 95% CI 0.96–1.25) were at higher risk of CHD. As an independent factor, CCHD was related to maternal age, DM, fetal gender, and maternal education level (all P &lt; 0.05). The prenatal ultrasound screening detection rate of CCHD was 97.59%, which was far higher than that of total CHD (51.67%) (P &lt; 0.001). The prenatal ultrasound diagnosis rate of CCHD was higher than that of simple CHD (P &lt; 0.001), but the coincidence rate in the ultrasound diagnosis of CCHD was lower than that of simple CHD (P &lt; 0.001). Prenatal genetic testing revealed chromosomal abnormalities in 25.62% (279/1089) of CHD cases with indications for a prenatal diagnosis.Conclusions: Maternal age, household registration and DM were related to CHD occurrence. Prenatal ultrasound screening is a highly effective method for CCHD diagnosis, and CHD fetuses should be closely evaluated to exclude chromosomal abnormalities.

Umbilical Cord Thrombosis: A Rare but Life-threatening Occurrence

Background: Thrombosis of umbilical vessels is a rare but life-threatening pregnancy complication. The correct diagnosis and clinical management of umbilical cord thrombosis remain a challenge. This study aimed to evaluate the meaningful clinical manifestations and features of umbilical cord thrombosis and its optimal management options.Methods: This retrospective study analyzed umbilical cord thrombosis cases enrolled from January 1, 2011, to May 31, 2021. Data were collected from medical archives where the diagnoses of all patients were established by histopathology.Results: A total of 66 patients with umbilical cord thrombosis were enrolled, including 20 patients with intrauterine fetal death and 6 with fatal labor induction in the second trimester. The overall incidence of umbilical cord thrombosis was 0.05% (66/123,746), and the incidence increased significantly in the last 2 years, reaching 0.19% in 2021. The chief complaint was decreased fetal movement (25/60) or nonreactive nonstress test (NST) (19/40). In the 20 patients with intrauterine stillbirth, 8 patients had ignored fetal movement and were referred to the hospital because of ultrasound findings of intrauterine stillbirth. Five patients were misdiagnosed with a single umbilical artery on prenatal ultrasound. Twenty patients underwent emergency cesarean section due to decreased fetal movement and unresponsive fetal monitoring; all neonates were alive. The gross examination of the placenta and cord revealed umbilical cord abnormalities in 26 patients (39.4%, 26/66). The pathological examination revealed venous, venous and arterial, and arterial thrombosis in 74.2%, 12.1%, and 13.6% of patients, respectively.Conclusions: The main manifestation of umbilical cord thrombosis was decreased or disappeared fetal movement. The importance of self-counting fetal movement should be emphasized to patients. The abnormalities in the umbilical cord are the main cause of this phenomenon. Focus on counting fetal movements, electronic fetal monitoring, and specific signs during a prenatal ultrasound can help early identification of umbilical cord thrombi. Emergency cesarean section is recommended to reduce the risk of interrupting the umbilical cord blood flow.