2020年 · 第02卷第04期

Objective: To evaluate the screening performance of noninvasive prenatal testing (NIPT) based on high-throughput massively parallel sequencing technology for the fetal XXY aneuploidies among pregnancies in Beijing of China. Methods: The study enrolled 26 913 consecutive pregnancies, 20-50 years old, who attended the Peking Union Medical College Hospital, Beijing, China, for prenatal screening from January 1, 2016 to December 31, 2019. Cell-free DNA was extracted from maternal peripheral blood to have a high-throughput massively parallel sequencing procedure. Cases with high-risk of fetal XXY were suggested to take invasive prenatal diagnosis (IPD) for confirmation. Maternal DNA sequencing was performed, if necessary, to find other potential factors that may lead to high-risk results of XXY by NIPT. Results: Among a cohort of 26 913 pregnant women, 34 were high-risk for fetal XXY, among which 30 accepted IPD while 4 declined. In those who accepted IPD, 19 cases were confirmed fetal XXY by chromosome karyotyping analysis while 11 were verified as false positive. Among the 19 confirmed fetal XXY cases, 14 elected pregnancy termination. For all the 34 high-risk cases, two were verified maternal sex chromosome aneuploidy. The calculated detection rate, positive predictive value, and false-positive rate of NIPT for fetal XXY in this cohort was 100.00% (19/19), 63.33% (19/30), and 0.04% (11/26 890), respectively. And the percentage of pregnancy termination was 73.68% (14/19). Conclusion: NIPT could be used as a potential method for fetal XXY screening, although the accuracy needs to be improved. As NIPT is not diagnostic, IPD is strongly recommended for those with high-risk results. For cases with discordance between NIPT and fetal karyotyping, maternal DNA sequencing would help to identify the cause of false-positive/false-negative results.

Objective: To assess the clinical features of fetal growth restriction (FGR) in women with hypertensive disorders of pregnancy in China. Methods: This is a retrospective cohort study. The clinical data of 4 451 women with hypertensive disorders of pregnancy were retrospectively collected from 11 tertiary hospitals across ten provinces in China during January 2015 to December 2015. The mean maternal age was (31.0±5.4) years old. Participants were divided into FGR group (n= 670) and non-FGR group (n= 3 781). The incidence and clinical features of FGR, and its correlation with gestational age, previous FGR history, 24-hour urinary protein excretion, and hemolysis, elevated liver enzyme and low platelet count (HELLP) syndrome were analyzed. Student’s t-test and Chi-square test were used when comparing clinical features between FGR and non-FGR groups. Results: The overall incidence of FGR was 15.1% (670/4 451). The FGR incidence was 22.4% (433/1 937) in women with severe preeclampsia and 18.6% (68/365) in women with chronic hypertension with superimposed preeclampsia, respectively. FGR was more prevalent in women who had preterm births than those who had term births (22.8% (432/1 898) vs. 9.3% (238/2 553), P < 0.001). It was also more prevalent in women with early-onset preeclampsia than those with late-onset preeclampsia (18.4% (189/1 025) vs. 14.0% (481/3 426), P= 0.001). Women with a previous FGR history had a significantly higher FGR incidence than those without an FGR history (66.7% (4/6) vs. 15.7% (250/1 596), P= 0.007). The presence of abnormal results of the umbilical artery Doppler (13% (87/670) vs. 2.4% (89/3 781), P < 0.001) and the middle cerebral artery Doppler (3.3% (22/670) vs. 0.4% (15/3 781), P < 0.001) was higher in the FGR group compared with the non-FGR group, while the presence of increased uterine artery resistance was not statistically different (1.5% (10/670) vs. 0.8% (29/3 781), P= 0.072). The FGR group delivered earlier than the non-FGR group ((35.3±3.0) weeks vs. (36.4±4.3) weeks, P < 0.001) with lower birth weight (1 731.0±574.5) g vs. (2 753.9±902.1) g, P < 0.001, higher fetal or neonatal death (9.4% (63/670) vs. 4.2% (157/3 781), P < 0.001), and higher cesarean section rate (82.5% (553/670) vs. 70.2% (2 656/3 781), P < 0.001). In the FGR group, more neonates had 5-minute Apgar score ≤7 (7.9% (53/670) vs. 3.9% (149/3 780), P < 0.001), with higher neonatal intensive care unit admission rate (48.1 % (322/670) vs. 23.3% (881/3 781), P < 0.001). More cases of HELLP syndrome occurred in the FGR group (6.9% (46/670) vs. 3.2% (122/3 781), P < 0.001). Women with FGR had heavier 24-hour urinary protein excretion than those without FGR ((3.9±3.7) g vs. (3.1±4.2) g, P= 0.005). Conclusion: In pregnancies with hypertensive disorders, increased risks of FGR are associated with preterm birth, birth before 34 weeks, and a previous FGR history. FGR is related to higher occurrence of abnormal uterine artery Doppler and umbilical artery Doppler. When hypertensive disorders is complicated by FGR, there appears to be higher maternal morbidity including higher rate of HELLP syndrome, cesarean section, and heavier proteinuria, as well as worse neonatal outcomes.

Objective: To explore the levels of fibroblast growth factor 23 (FGF23) during pregnancy and its relationship with intrauterine growth restriction (IUGR). Methods: Pregnant rats were classified into an ad libitum rat chow group (ad libitum rat chow, AD group, n = 25) and an undernutrition group (50% of their daily food requirement, UN group, n= 25). The levels of maternal serum FGF23, tissue homogenate FGF23, and bone gla protein in fetal rats, and placental FGF23 mRNA and protein expression were examined by enzyme-linked immunosorbent assay, real-time qPCR analysis respectively. Finally, the effect of recombinant FGF23 on the viability of MG-63 cells was determined by cell proliferation assay. Data were analyzed with independent two-tailed t test and one-way analysis of variance. Spearman rank-order correlation coefficients (continuous variables) was performed to determine the relationship of results. Results: The diet restriction induced IUGR in rat offsprings, and the UN group exhibited a significantly lower FGF23 level (P < 0.05, n= 5). The FGF23 level was increased and peaked in maternal serum on gestation day (GD) 15, but peaked in fetal and placenta on GD20. Moreover, the tissue homogenate levels of FGF23 and bone gla protein in fetal rats in both groups were positively correlated (r= 0.923, P < 0.05; r= 0.925, P < 0.05, respectively, n = 15), FGF23 was localized to both decidual and labyrinth zones, with remarkably higher expression on GD20, P < 0.05, n= 5. In vitro, recombinant human FGF23 enhanced MG-63 cell viability, P < 0.05, n= 5. Conclusion: Prenatal undernutrition could decrease the FGF23 expression in fetal rats caused by the mother through the placenta, and induced the IUGR and hindered the ossification. And the FGF23 levels are peaked on GD15 mother but peaked on GD20 placenta and fetuses, these might be associated with the over compensation of maternal placenta on GD20.

Over the past 50 years, the scope and extent of prenatal diagnosis and screening for genetic disorders have improved geometrically. There has been a pendulum like swing from testing to screening back and forth as new technologies emerge. The concurrent developments of cell free fetal DNA analysis of maternal blood has dramatically changed patient’s choices towards screening. However, with the use of array comparative genomic hybridization of fetal DNA that requires diagnostic procedures (Chorionic villus sampling and amniocentesis), much more extensive diagnosis can be obtained. Until noninvasive methods can replicate what can be done with diagnostic procedures there still will be a "price to be paid" for opting for the non-invasive methods.

Intraamniotic infection (IAI) or chorioamnionitis is a common cause of preterm birth and may cause adverse neonatal outcomes, including neonatal pneumonia, respiratory distress, meningitis, sepsis, and death. Maternal morbidities from intraamniotic infection include dysfunctional labor requiring increased intervention, cesarean birth, postpartum uterine atony with hemorrhage, endometritis, peritonitis, sepsis, adult respiratory distress syndrome and, rarely, death. Chorioamnionitis can result from an ascending infection, iatrogenic causes or transplacental passage from maternal blood-borne infections. The clinical findings of chorioamnionitis include maternal fever (≥38 °C), maternal (>100 beats per minute) and/or fetal tachycardia (>160 beats per minute), maternal leukocytosis on complete blood count (>15 000 cells/mm3), and uterine tenderness and/or purulent and/or foul-smelling amniotic fluid. The management of chorioamnionitis mainly includes antibiotic therapy and delivery. Women with previable preterm premature rupture of membranes should be offered realistic counseling from a multidisciplinary approach. The separation of the mother and the fetus to preserve the life of the mother should prioritize delivery methods that result in a living fetus if possible, with appropriate neonatal resuscitation available.

Sepsis, which is life-threatening organ dysfunction resulting from a dysregulated host response to infection, remains a major cause for the admission of pregnant women to the intensive care unit and is one of the leading causes of maternal morbidity and mortality. The obstetric causes include uterine infection, septic abortion, and wound infection. The non-obstetric causes include pyelonephritis and pneumonia. Maternal sepsis may also be from obstetrical critical illness, such as obstetric severe hemorrhage, obstetric (amniotic fluid/pulmonary) embolism, acute fatty liver of pregnancy, and congestive heart failure, cardiopulmonary arrest, and major trauma. The most commonly reported pathogens in maternal sepsis include Escherichia coli, Streptococcus, Staphylococcus, and other gram-negative bacteria. Maternal sepsis may cause intrauterine infection, which results in (1) preterm premature rupture of membranes or preterm labor or birth, (2) cerebral white matter damage or cerebral palsy or neurodevelopmental delay, (3) stillbirth, (4) early- or late-onset sepsis, and (5) perinatal death. The "Hour-1 bundle" should be initiated within the first hour of the recognition of sepsis. The use of early, appropriate antibiotics is crucial in the management of maternal sepsis. Fetal status should be monitored. Appropriate and early source control should be provided. The decision for delivery is often quite complex and should be individualized to each patient’s clinical scenario while taking into consideration the suspected source of infection, maternal status, fetal well-being, and gestational age. Extracorporeal membrane oxygenation has been increasingly used in refractory sepsis during pregnancy and the puerperium.

Fetal cardiac rhabdomyoma is associated with tuberous sclerosis complex (TSC) which is an autosomal dominant hereditary neurocutaneous disease with an incidence of approximately 1 in 5 000 to 10 000 live birth. It is caused by mutations in the TSC1 or TSC2 gene, de novo mutations accounting for approximately 80% of TSC cases, which can involve multiple organs and systems such as the heart, brain, kidney, lung, skin, and so on. Cardiac rhabdomyoma is the most common fetal heart tumor, accounting for about 60% of cases. It is closely related to TSC and may be the only manifestation of TSC which occurs during pregnancy. This study retrospectively analyzed the clinical data of a neonate with TSC diagnosed with fetal cardiac rhabdomyomas and confirmed by amniocentesis prenatal diagnosis as gene testing TSC1 gene positively. The parents had no such mutation. However, due to the influence of the sudden coronavirus disease 2019 (COVID-19) epidemic, the TSC genetic test report was not obtained until 38 weeks of pregnancy. Multiple hypo-pigmented spots (diameter >5 mm) were found immediately after birth. The characteristic cardiac feature of TSC is a rhabdomyoma and the diagnosis of TSC is based upon genetic testing and multiple ultrasound examinations or magnetic resonance imaging. Most patients with TSC have epilepsy, and one-half or more have cognitive deficits and learning disabilities. So rigorous follow-up will continue for the case we reported.

Harlequin ichthyosis is a severe autosomal recessive skin disorder. Most deaths occur within the first few days after birth, and the survivors still have severe chronic skin disease throughout their lives. Almost all cases were associated with a pathogenic variant of adenosine triphosphate binding cassette transporter, subfamily A, member 12 (ABCA12) gene. We described a case of HI diagnosed by ultrasound examination during the second-trimester and genetic diagnosis reveal two novel heterozygous ABCA12 mutations c.2563-2570delinsGGCAATT, p.(Leu855Glyfs*13), and c.6116delT, p.(Met2039Argfs*8) by the next-generation DNA sequencing, which further enriched our understanding of the pathogenic variation of ABCA12 gene.

Breast neuroendocrine carcinoma is a rare entity. It constitutes less than 0.5% of breast malignancies, and is usually diagnosed in older women. The occurrence of this type in young patients during pregnancy is extremely rare. Only 2 cases were previously reported. Both were diagnosed at earlier stage with the appearance of a palpable breast mass. Hereby, we present the case of a young patient at 28 weeks’ gestation admitted for severe diffuse back pain and neurologic deficit due to spinal cord compression at the level of C5 vertebra, and nerve root compression at the level of L5 vertebrae. To the best of our knowledge, this is the first case of oncologic emergency during pregnancy due to a metastatic poorly differentiated breast carcinoma with neuroendocrine differentiation in the absence of a detectable primary focus of malignancy in the breast. We also discuss the management and the obstetrical outcome of this patient.

On April 3, 2020, a 37-year-old woman successfully completed heart valve replacement after cesarean section 67 hours in the First Affiliated Hospital of Harbin Medical University.The woman underwent the mechanical mitral valve replacement in the same hospital 10 years ago. She used low molecular weight heparin instead of warfarin, when she realized her pregnancy. On March 25, 2020 (28+5 weeks of gestation), due to New York Heart Association class IV, severe pneumonia, type I respiratory failure, the patient was admitted to the hospital for treatment. Three days later, she discharged herself from hospital by refusing the cesarean section. The next day she was re-admitted to the ward because of the worsen symptoms and oliguria. Cesarean section was performed 50 hours after admission. The neonate was 1 400 g; Apgar score was 5 in 1 minute, 8 in 5 minutes, transferred to neonatal intensive care unit. Because of the unrecovered heart function, she was confirmed stuck mechanical prosthetic mitral valves. On April 3, 2020, through multi-disciplinary cooperation, the patient was safe without any life-threatening emergency. Eleven days after the replacement, the patient was discharged smoothly, so was the neonate 33 days after delivery.