Impact of the COVID-19 pandemic on congenital diaphragmatic hernia patients: a single-center retrospective study.

PURPOSE: To investigate the impact of COVID-19 on the treatment of children with congenital diaphragmatic hernia (CDH). METHODS: We retrospectively collected and compared the data of patients with CDH admitted between January 1, 2020 and December 31, 2021(study group) with the CDH patients admitted before the pandemic between January 1, 2018 and December 31, 2019 (control group). RESULTS: During the pandemic, 41 patients with CDH diagnosed prenatally were transferred to our hospital, and 40 underwent surgical repair. The number of patients treated in our hospital increased by 24.2% compared with the 33 patients before the pandemic. During the pandemic, the overall survival rate, postoperative survival rate and recurrence rate were 85.4%, 87.5% and 7.3%, respectively, and there were no significant differences compared with the control group (75.8%, 83.3% and 9.1%, respectively). The average length of hospital stay in patients admitted during the pandemic was longer than that in the control group (31 days vs. 16 days, P < 0.001), and the incidence of nosocomial infection was higher than that in the control group (19.5% vs. 3%, P = 0.037). CONCLUSIONS: CDH patients confirmed to be SARS-CoV-2 infection-free can receive routine treatment. Our data indicate that the implementation of protective measures during the COVID-19 pandemic, along with appropriate screening and case evaluation, do not have a negative impact on the prognosis of children.

Adducted thumb as an isolated morphologic finding: an early sonographic sign of impaired neurodevelopment: A STROBE compliant study.

Fetal adducted thumbs have been described in association with hydrocephalus and other abnormalities, but in cases without other structural malformations the determination of prognosis and recurrence risk is challenging. The aim of our study is to analyze the characteristics, natural history, and postnatal outcome of such cases.A retrospective study was conducted over a period of 4 years in a tertiary referral center. All fetuses diagnosed as adducted thumbs without other structural malformations comprised the study group. Prenatal sonographic features and neonatal outcome are documented.There were 4 cases of fetal adducted thumbs diagnosed during the study period. No cases demonstrated other structural malformations throughout the gestation. A smaller head was noted in 2 cases during the follow-up, and all cases presented with polyhydramnios on the first or ensuing scans. Three cases died after birth due to swallowing or breathing difficulty, and the surviving 1 showed convulsion and mental retardation.Fetal adducted thumb might be an early and specific sonographic marker of impaired neurodevelopment. Close follow-up and genetic investigation should be performed in these cases. Ultrasound examination plays an important role in the prenatal diagnosis and counseling of cases without detailed prenatal genetic analysis.

Genetic counseling, prenatal screening and diagnosis of Down syndrome in the second trimester in women of advanced maternal age: a prospective study.

BACKGROUND: The incidence of autosomal trisomy in livebirths is strongly dependent on maternal age. Special consideration is given to the provision of prenatal screening and cytogenetic testing to women of advanced maternal age (AMA). The aim of this study was to evaluate the effectiveness of second trimester prenatal screening and amniocentesis for Down syndrome (DS) and compare the trends of choice of screening and amniocentesis among AMA women. METHODS: A total of 5404 AMA patients with natural singleton pregnancy were recruited for this prospective study from January 2008 to December 2010. The gestational weeks were from 15 weeks to 20(+6) weeks. The patients referred were grouped into a screening group (2107 cases) and an amniocentesis group (3297 cases) by their own decision. The prevalence of DS was compared between the two groups by chi-square test. Choice rates for each maternal age with trends were compared by regression analysis. RESULTS: There were 18 cases of fetal DS detected in the screening group with a prevalence of 8.54‰ (18/2107). Twenty-five cases of fetal DS were diagnosed in the amniocentesis group with a prevalence of 7.58‰ (25/3297). No statistical difference was observed in the prevalence of DS between the screening and amniocentesis group (P = 0.928). The invasive testing rate for DS in the amniocentesis group was 5.54 times higher than that of the screening group (1/131.88 vs. 1/23.78). With the increase of the maternal age, the choice of amniocentesis increased while the choice of the screening showed an opposite trend. The choice of the AMA women between the screening and amniocentesis was significantly age relevant (P = 0.012). CONCLUSIONS: The second trimester serum screening in combination with maternal age was more effective than maternal age alone to screen for DS. We suggest educating the patients by recommending AMA women be informed of both screening and amniocentesis options.

[Management of pregnancy with myasthenia gravis: 7 cases report].

OBJECTIVE: To discuss the interaction of pregnancy and myasthenia gravis (MG) and the management of pregnancy with MG. METHODS: Seven cases of pregnancy with MG in Peking Union Medical College Hospital were analyzed retrospectively, with respect to the therapy of MG, pregnancy complications and outcomes. RESULTS: Totally 38,683 pregnant women were admitted to Peking Union Medical College Hospital between Oct. 1983 and Oct. 2010. Among them there were 9 patients suffered from MG, with the incidence of 0.023%. Two pregnancies were terminated because of personal reasons, and seven continued. (1) Onset of MG: in the 7 cases, 6 were diagnosed before conception, with the mean course of 5.9 years. The other one occurred in the third trimester. (2) MANAGEMENT: all the cases were under close surveillance during pregnancy. Four women took thymectomy before conception, and one of them kept taking medication after surgery. In those who received thymectomy, 3 cases remained stable and 1 case worsened during pregnancy. The latter one took medication at 33 weeks, and continued to full term. MG exacerbated in the other three women who had not undergone thymectomy before conception. Among them, one woman complicated with systemic lupus erythematosus and lupus nephritis delivered the baby at 31 weeks. (3) Delivery and neonatal outcomes: cesarean deliveries were performed in 5 cases and the other two underwent vaginal deliveries. All the newborns were admitted to neonatal intensive care unit for surveillance. There were three smaller than gestational week (SGA) infants. No MG was observed in newborns. CONCLUSIONS: Patients with MG should have an overall evaluation before conception. The course of MG during pregnancy is unpredictable. They may get a promising outcome under the control of a multidisciplinary team including obstetricians and neurologists. Newborns should be carefully monitored for sings of transitory MG in the department of pediatrics.

[Clinical analysis of pregnancies after vaginal radical trachelectomy].

OBJECTIVE: To explore the pregnancy outcome and obstetric management of pregnancy and delivery after vaginal radical trachelectomy (VRT). METHODS: Forty-two cases of VRT from December 2003 to May 2012 in Peking Union Medical College Hospital were analyzed retrospectively. Among them ten cases got pregnant successfully. RESULTS: The average age of patient at VRT surgery was (30.6 ± 3.7) years old and average follow-up time was 29.5 months. There were 31 patients attempted conception. Ten of them got fourteen conceptions successfully. Overall conception rate was 45% (14/31). There were four cases of first trimester abortion. Among them, two were miscarriage, two were elective abortion. There was one case of ectopic pregnancy operation and non of second trimester loss. Nine cases reached the third trimester. The total preterm delivery rate was 4/9. There were two cases delivered before 32 gestational weeks (2/9). Cesarean section was performed through a transverse incision in all of nine cases. No uterine rupture and postpartum hemorrhage occurred. All newborns had good outcomes. The average follow-up time after postpartum was 22.9 months. All cases were disease-free. CONCLUSIONS: The conception rate of patients after VRT in our series is 45%. The preterm birth rate of pregnancy after VRT is higher. Routine cerclage of cervix during VRT procedure and pregnancy is not necessary. Cesarean section shortly after full term pregnancy through a transverse incision should be considered as a suitable and safe procedure.

Current situation and development of prenatal diagnosis in China.

Prenatal screening and diagnosis are major methods for control of birth defects, which is a very important problem in China. Here, we review current situation and development of prenatal screening and diagnosis in mainland China, including prenatal screening and prenatal diagnosis of fetal chromosome abnormalities, non-invasive prenatal diagnostic techniques and prenatal diagnosis of monogenic diseases, polygenic disease and congenital metabolic diseases. We also discuss epidemiology of birth defects and genetic diseases in China and related ethical issues of prenatal diagnosis.

[Second trimester maternal serum screening for Down's syndrome in women of advanced maternal age: a multi-center prospective study].

OBJECTIVE: To evaluate the performance characteristics of the second trimester double test for the detection of fetal Down's syndrome (DS) in women of advanced maternal age (AMA). METHODS: We undertook a prospective nation-wide multi-centered study and chose alpha-fetoprotein (AFP) and free beta-subunit of human chorionic gonadotrophin (free beta-hCG) as the serum markers. Between May 2004 and September 2006, 12 centers participated in the collection and analysis of maternal serum AFP and free beta-hCG. Patients with an increased risk of DS (> or = 1/270) were offered genetic amniocentesis. Follow up of the outcome of all pregnancies was obtained. Patients were divided into two groups, the AMA group and the non-AMA group and the screening efficiency was evaluated in both groups. RESULTS: A total of 66 132 singleton pregnancies were included in the study, and there were 3610 (5.46%) AMA women. The median maternal age of AMA women was 36.8years (35 - 47 years). At a cut-off of 1/270, in the AMA group, the number of positive cases screened was 727 and 22 cases of fetal DS were detected; the number of negative cases screened was 2883, and no fetal DS was found. In the non-AMA group, the number of positive cases screened was 4743 and 69 cases of fetal DS were detected; the number of negative cases screened was 57 779, and 6 cases of fetal DS were diagnosed postnatally. In AMA group, the detection rate (DR), false positive rate (FPR) and odds of being affected given a positive result (OAPR) were 100%, 19.7% and 3.0% respectively. In the non-AMA group, the DR, FPR and OAPR were 92.0%, 7.5% and 1.5% respectively. CONCLUSION: The double-marker test using AFP and free beta-hCG is an effective screen strategy for second-trimester detection of Down syndrome in AMA women.

[Second trimester maternal serum screening for Down's syndrome in mainland China: a multi-center prospective study].

OBJECTIVE: To evaluate the performance characteristics of the second trimester double-marker test for the detection of fetal Down's syndrome in mainland China. METHODS: This prospective national multi-centered study used alpha-fetoprotein (AFP) and free beta-subunit of human chorionic gonadotrophin (free beta-hCG) as the serum markers. From May 2004 to September 2006, 11 centers participated in the collection and analysis of maternal serum AFP and free beta-hCG between 14 and 20(+6) weeks of pregnancy. The screening results were calculated using the standard algorithm based on the standard database provided with the analytic software. Patients with an increased risk of Down's syndrome pregnancy (> or = 1/270) were offered genetic amniocentesis. Outcomes of all pregnancies were obtained. RESULTS: A total of 66 132 singleton pregnancies were included in the study. The median maternal age was 27 years. At a cut-off of 1 in 270, the detection rate (DR) based on a Caucasian database was 72% corresponding to a false positive rate (FPR) of 5%, and the DR based on the Chinese database was raised to 76% corresponding to an FPR of 5%. CONCLUSION: The double-marker test using AFP and free beta-hCG is an effective screen strategy for second-trimester detection of fetal Down's syndrome in mainland China. Ethnic variance exists between the Caucasian and Chinese populations. The accuracy of screening is increased by the use of race-specific medians.

Changes of clinical features in hydatidiform mole: analysis of 113 cases.

OBJECTIVE: To investigate the changes of the clinical features of hydatidiform mole. STUDY DESIGN: A total of 113 cases of hydatidiform mole treated in Peking Union Medical College Hospital during 1989-2006 were reviewed retrospectively, and a comparison was made to historic data from 1948-1975 using the chi2 test. RESULTS: The median age was 28 years (range, 20-55). The median gestational age was 90.2 days. Vaginal bleeding remains the most common presenting symptom, occurring in 94 of 113 cases (83.2%). Of 113 cases, 52 (46%) presented with excessive uterine size. Preeclampsia, hyperemesis, hemoptysis and theca lutein cysts occurred in 4 of 113 (3.5%), 12 of 113 (10.6%), 4 of 113 (3.5%) and 19 of 113 cases (16.8%), respectively. The incidence of postmolar trophoblastic neoplasia was 21% (24 of 113). Compared to historic data, the incidence of vaginal bleeding and preeclampsia were statistically lower (p < 0.005). The incidence of postmolar gestational trophoblastic neoplasia was increased moderately without statistical significance compared to historic data. CONCLUSION: Because of the wide use of ultrasonography and serum human chorionic gonadotropin test, current patients with hydatidiform mole have been diagnosed earlier in gestation and the clinical features have changed. Patterns of medical practice should be changed as well.

[Prenatal diagnosis for hereditary deaf families assisted by genetic testing].

OBJECTIVE: To provide prenatal diagnosis for deaf families, which the first child was confirmed to be hereditary deafness caused by gap junction beta-2 (GJB2) or SLC26A4 (PDS) mutation, to avoid another deaf birth in these families. METHODS: Eight deaf families joined in this study. Each family had one child with severe to profound hearing loss while parents had normal hearing except a deaf father from family 8; mothers had been pregnant for 6-28 weeks. Genetic testing of GJB2, SLC26A4 and mitochondrial DNA (mtDNA) A1555G mutation were firstly performed in probands and their parents whose DNA was extracted from peripheral blood, and then prenatal testing was carried out in the fetus whose DNA was extracted from different fetus materials depending on the time of gestation. RESULTS: The probands from family 1-4 were found to carry homozygous or compound GJB2 mutations while their parents carried corresponding heterozygous GJB2 mutations. The probands from family 5-8 and the deaf father from family 8 were found to carry compound SLC26A4 mutations while their parents and the mother from family 8 carried a single SLC26A4 mutation. Prenatal testing showed that the fetuses from family 1, 5, 8 only carried the paternal mutation and the fetuses from family 2, 3, 6 didn't carry any GJB2 or SLC26A4 mutations. The new born babies from these six families all had normal hearing revealed by new born hearing screening. However, the fetuses from family 4,7 carried the same mutations with probands in each family. The parents from family 4, 7 decide to terminate pregnancy. CONCLUSION: Prenatal diagnosis assisted by genetic testing can provide efficient information about hearing condition of their offsprings.

[Study on the correlation of serum folate and red blood cell folate level with birth defects and unexplained recurrent pregnancy loss].

OBJECTIVE: To understand the correlation of lower serum folate, and red blood cell (RBC) folate level with birth defects including unexplained recurrent pregnancy loss, and to evaluate the role of RBC folate level as a suitable marker for folate supplement. METHODS: Two hundred and ninety-nine non-pregnant women at child-bearing age with a birth defect history were selected as birth defect group. The levels of serum and RBC folate, and serum vitamin B(12) were determined. By comparing with the group of non-pregnant women at child-bearing age without any birth defect history (control group), we evaluated the correlation between lower serum folate, RBC folate level and main kinds of birth defects including unexplained recurrent pregnancy loss. And the levels of serum and RBC folate of birth defect group were also determined and compared before and after oral folate intake (5 mg/d) for one month. RESULTS: The serum folate level of birth defect group was not different from the control group (17 - 26 vs 14 nmol/L, P > 0.05). The RBC folate level of birth defect group except the urinary defect was significantly lower compared with the control group (233 - 547 vs 689 nmol/L, P < 0.05). After the oral folate intake (5 mg/d), the serum folate level of unexplained recurrent pregnancy loss group and neural tube defects group were significantly increased than before [(22 +/- 9) vs (27 +/- 12) nmol/L, (19 +/- 10) vs (25 +/- 18) nmol/L; P < 0.05]. The RBC folate level of unexplained recurrent pregnancy loss group and congenital heart defect group were significantly increased than before [(374 +/- 275) vs (567 +/- 397) nmol/L, (322 +/- 205) vs (527 +/- 351) nmol/L, P < 0.05]. CONCLUSION: RBC folate level is more closely correlated than serum folate level with the incidence of main birth defect.

[Postnatal and prenatal diagnosis of mucopolysaccharidosis type II (Hunter syndrome)].

OBJECTIVE: Mucopolysaccharidosis type II (MPS II, Hunter syndrome, OMIM 309900) is an X-linked recessive lysosomal storage disease resulting from a deficiency of iduronte-2-sulphate sulphatase (IDS). The present study aimed to establish an enzyme assay method for IDS activity for carrying out postnatal and prenatal diagnosis of MPS II by means of IDS activity assay on plasma, uncultured chorionic villi (CV) and cultured amniotic fluid cells (AF cell) using a new synthesized substrate. METHODS: A fluorigenic substrate (4-methylumbelliferyl-alpha-iduronate-2-sulphate, MU-alpha-Idu-2S) was used for the assay of IDS activity. IDS activity in plasma was determined for diagnosis of the proband. Prenatal diagnosis in 10 pregnancies at risk was carried out according to IDS activity on uncultured CV at 11th week or on cultured AF cell at 18th week of gestation. At the same time, IDS activity was also determined in the maternal plasmas to observe the change of IDS activity in pregnancy. The fetal sex determination was performed by PCR amplification of the ZFX/ZFY genes. RESULT: The IDS activity in plasma of normal controls and obligate heterozygotes were 240.2 - 668.2 nmol/(4 hxml) and 88.7 - 547.9 nmol/(4 hxml), respectively, while the enzyme activities in plasmas were in the range of 0.3 - 18.6 nmol/(4 hxml) in affected male. The IDS activities were 37.2 - 54.9 nmol/(4 hxmg protein) and 21.4 - 74.4 nmol/(4 hxmg protein) in CV and cultured AF cells respectively. Out of 50 suspected cases, 46 were diagnosed as having MPS II and 4 were excluded. Prenatal diagnosis was performed on 10 pregnancies at risk. Four of 5 male fetuses [IDS activity were 4.7, 1.8, 7.0 nmol/(4hxmg protein) in CV, 0.6 nmol/(4 hxmg protein) in AF cell] were diagnosed as having MPS II and the other 5 fetuses were normal females [IDS activity were: 48.7, 5.9, 25.2 nmol/(4 hxmg protein) in CV, 55.2, 40.9 nmol/(4 hxmg protein) in AF cell]. Increased IDS activity was observed in plasma of the pregnant women with unaffected fetuses, while the IDS activity decreased in pregnancies with affected fetuses. IDS activity of one female fetus was very low [5.9 nmol/(4 hxmg protein)], but the IDS activity in maternal plasmas increased, this fetus was a normal female. CONCLUSIONS: The method using a synthesized fluorigenic 4-methylumbelliferyl-substrate was a sensitive, rapid and convenient assay of IDS activity and was reliable for early prenatal diagnosis. Determination of fetal sex would be helpful in excluding the female fetus with low IDS activity from being considered as an affected male fetus. It would be further helpful if IDS activity in maternal plasma was taken into account.

[Detection of the gene-deleted female carriers of Duchenne/Becker muscular dystrophy using a fluorescent in situ hybridization based method].

OBJECTIVE: To set up a fluorescent in situ hybridization (FISH) based method to detect the gene-deleted female carriers of Duchenne/Becker muscular dystrophy (DMD/BMD). METHODS: Multiplex polymerase chain reaction was used to identify the gene deletion DMD/BMD probands and their female relatives were checked by double-color FISH. RESULTS: Two probands whose exon 46 of dystrophin gene was deleted, one had a positive pedigree and the other was a sporatic patient. In the case of the positive pedigree, four carriers were detected. In the case of the sporatic family, FISH showed that the mother of the proband was a somatic mosaicism. CONCLUSION: Combined with multiplex PCR, double-color FISH is a simple, fast, directly visual and accurate method. It is feasible to identify the carrier status of the female relatives of the gene deletion DMD/BMD probands. The detection of the somatic mosaicism is a prominent feature of FISH.

[Prenatal diagnosis and clinical management of a twin pregnancy consisting of a complete mole and coexisting fetus].

OBJECTIVE: To discuss the differential diagnosis of the hydatidiform mole and a coexisting fetus, to study the prenatal diagnosis and the clinical management of a twin pregnancy consisting of a complete mole and coexisting fetus (CMCF). METHODS: Two cases of CMCF were reported retrospectively. RESULTS: In the first case, the hydatidiform mole and a coexisting fetus was found by B mode ultrasound at the 10th gestational week, the patient asked to terminate the pregnancy. The interphase FISH and karyotype analysis of the normal villi and the mole showed both of them were diploid, thus the CMCF was diagnosed. In the second case, the hydatidiform mole and a coexisting fetus was found by B mode ultrasound at the 21st gestational week. Transabdominal chorionic villi sampling and amniocentesis was performed, interphase FISH and karyotype analysis of the mole and the amniotic fluid showed both of them were diploid, thus the CMCF was diagnosed prenatally. The pregnancy was continued and premature rupture of membrane happened at the 28th gestational week, the cesarean section was performed. The neonate was healthy. The karyotype analysis of the placenta and the neonate was accordant with the prenatal diagnosis. CONCLUSIONS: As long as the hydatidiform mole and a coexisting fetus was found the prenatal diagnosis must be performed in order to differentiate the CMCF and the partial hydatidiform mole (PHM). The transabdominal chorionic villi sampling and the amniocentesis were ideal methods, interphase FISH and karyotype analysis of the mole and the amniotic fluid should be performed. If both of them were diploid, the CMCF could be diagnosed. The clinical management of CMCF should be done individually. If both of them were triploid, the PHM could be diagnosed.