Association of maternal weight gain in early pregnancy with congenital heart disease in offspring: a China birth cohort study.

OBJECTIVES: Little study has reported the association of maternal weight gain in early pregnancy with fetal congenital heart disease (CHD). We aimed to explore the potential relationship based on a China birth cohort while adjusting by multiple factors. DESIGN: Cohort study. SETTING: China birth cohort study conducted from 2017 to 2021. PARTICIPANTS: The study finally included 114 672 singleton pregnancies in the 6-14 weeks of gestation, without missing data or outliers, loss to follow-up or abnormal conditions other than CHD. The proportion of CHD was 0.65% (749 cases). PRIMARY AND SECONDARY OUTCOME MEASURES: Association between maternal pre-pregnancy weight gain and CHD in the offspring were analysed by multivariate logistic regression, with the unadjusted, minimally adjusted and maximally adjusted methods, respectively. RESULTS: The first-trimester weight gain showed similar discrimination of fetal CHD to that period of maternal body mass index (BMI) change (DeLong tests: p=0.091). Compared with weight gain in the lowest quartile (the weight gain less than 0.0 kg), the highest quartile (over 2.0 kg) was associated with a higher risk of fetal CHD in unadjusted (OR 1.36, 95% CI: 1.08 to 1.72), minimally adjusted (adjusted OR (aOR) 1.29, 95% CI: 1.02 to 1.62) and maximally adjusted (aOR 1.29, 95% CI: 1.02 to 1.63) models. The association remains robust in pregnant women with morning sickness, normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with folic acid (FA) and/or multivitamin supplementation. CONCLUSIONS AND RELEVANCE: Although the association of maternal pre-pregnancy weight gain on fetal CHD is weak, the excessive weight gain may be a potential predictor of CHD in the offspring, especially in those with morning sickness and other conditions that are routine in the cohort, such as normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with FA and/or multivitamin supplementation.

Intra-abdominal umbilical venous diameter and abdominal circumference discordance at 15-20 weeks' gestation: simple markers in transverse abdominal plane to predict adverse pregnancy outcomes in monochorionic diamniotic twins.

PURPOSE: This study aimed to investigate the association between simple markers in fetal abdominal plane, intra-abdominal umbilical venous diameter (DIUV) and abdominal circumference (AC) discordance at 15-20 weeks' gestation, and adverse pregnancy outcomes in monochorionic diamniotic (MCDA) twins. METHODS: We performed a retrospective analysis of MCDA twins with two live fetuses examined at 15-20 weeks from Jun 2020 to Dec 2021 at Beijing Obstetrics and Gynecology Hospital. Measurement of fetal AC and DIUV was performed according to standard protocols. Twin pregnancies with major fetal structural anomalies, chromosomal abnormalities, miscarriage, and twin reversed arterial perfusion sequence were excluded. DIUV and AC discordance in MCDA twins with an adverse pregnancy outcome was compared with a normal pregnancy outcome. Furthermore, the performance of DIUV and AC discordance in predicting adverse pregnancy outcomes in MCDA twins was assessed. RESULTS: A total of 105 women with MCDA twin pregnancies were enrolled, contributing 179 visits. Adverse pregnancy outcomes occurred in 33.3% (35/105) of cases in our study. The intra-observer and inter-observer intraclass correlation coefficient (ICC) of both AC and DIUV were very good or excellent. There was no statistical difference in AC and DIUV discordance (%) between 15-16, 17-18, and 19-20 weeks (χ2 = 3.928, P = 0.140; χ2 = 2.840, P = 0.242). Both AC and DIUV discordance were greater in twins with adverse pregnancy outcomes than that in twins with normal pregnancy outcome at each pregnancy periods. Both AC discordance (OR 1.2, 95% CI 1.1-1.3) and DIUV discordance (OR 1.2, 95% CI 1.1-1.2) were associated with adverse pregnancy outcomes. The AUC for predicting adverse pregnancy outcomes by AC discordance was 0.75 (95% CI 0.68-0.83), with a sensitivity of 58.7% (95% CI 51.9-64.5) and a specificity of 86.2% (95% CI 81.7-88.4). The AUC for predicting adverse pregnancy outcomes by DIUV was 0.78 (95% CI 0.70-0.86), with sensitivity and specificity of 65.1% (95% CI 58.1-70.3) and 86.2% (95% CI 81.7-88.4), respectively. CONCLUSIONS: The AC discordance and DIUV discordance could predict adverse pregnancy outcomes in MCDA twins. When these simple markers occurred, intensive surveillance was recommended.

Prenatal ultrasound findings, genetic testing, and literature review of Isolated left subclavian artery.

BACKGROUND: The occurrence of Isolated left subclavian artery (ILSA) is relatively rare, ILSA is caused by the persistence of the dorsal segment of the sixth left arch, with regression of the fourth arch artery and interruption of the left dorsal aorta at the distal end of the seventh intersegmental artery on the left side during embryonic development. The left subclavian artery is connected to the pulmonary artery through an arterial duct, which can be closed or unobstructed. This abnormality can lead to congenital subclavian steal syndrome and vertebrobasilar artery insufficiency. CASE PRESENTATION: We reported three fetuses with ILSA and intracardiac malformation. Among them, one case was suspected to be diagnosed with ILSA by echocardiography, while the other two cases were not diagnosed, but were accidentally discovered during autopsy. We have also conducted a literature review of its prenatal screening, diagnosis, management, and outcomes. Our three cases were tested by WES-Trio (whole exome sequencing). Worldwide, the ILSA cases reported in English literature have not been detected by WES. And likely pathogenic results were found in our two cases. Although it could not explain the intracardiac malformation we found, it will help to explore the etiology in the future. CONCLUSIONS: Prenatal echocardiography detection and diagnosis of ILSA is a new challenge, which has different effects on the prognosis of the fetus. When finding intracardiac malformation with right aortic arch, we need to perform an unconventional view of ultrasound scanning and combine with CDFI to find the origin of the left subclavian artery. Although we cannot find the cause of the disease temporarily, but our genetic results can help prenatal genetic counseling.

Diagnostic Value of Chromosomal Microarray Analysis for Fetal Congenital Heart Defects with Different Cardiac Phenotypes and Extracardiac Abnormalities.

(1) Background: The objective of this study was to investigate the diagnostic value of chromosomal microarray analysis (CMA) for congenital heart defects (CHDs) with different cardiac phenotypes and extracardiac abnormalities (ECAs) and to explore the pathogenic genetic factors of CHDs. (2) Methods: We collected fetuses diagnosed with CHDs by echocardiography at our hospital from January 2012 to December 2021. We analyzed the CMA results of 427 fetuses with CHDs. We then categorized the CHD into different groups according to two dimensions: different cardiac phenotypes and whether it was combined with ECAs. The correlation between the numerical chromosomal abnormalities (NCAs) and copy number variations (CNVs) with CHDs was analyzed. Statistical analyses, including Chi-square tests and t-tests, were performed on the data using IBM SPSS and GraphPad Prism. (3) Results: In general, CHDs with ECAs increased the detection rate for CA, especially the conotruncal defects. CHD combined with the thoracic and abdominal walls and skeletal, thymic and multiple ECAs, were more likely to exhibit CA. Among the CHD phenotypes, VSD and AVSD were associated with NCA, while DORV may be associated with NCA. The cardiac phenotypes associated with pCNVs were IAA (type A and B), RAA, TAPVC, CoA and TOF. In addition, IAA, B, RAA, PS, CoA and TOF were also associated with 22q11.2DS. The length distribution of the CNV was not significantly different between each CHD phenotype. We detected twelve CNV syndromes, of which six syndromes may be related to CHDs. The pregnancy outcome in this study suggests that termination of pregnancy with fetal VSD and vascular abnormality is more dependent on genetic diagnosis, whereas the outcome in other phenotypes of CHDs may be associated with other additional factors. (4) Conclusions: CMA examination for CHDs is still necessary. We should identify the existence of fetal ECAs and specific cardiac phenotypes, which are helpful for genetic counseling and prenatal diagnosis.

A case report of serpentine-like syndrome and review of literature.

BACKGROUND: Serpentine-like syndrome (SLS) is a rare foetal abnormality, characterized by brachioesophagus, secondary intrathoracic stomach and vertebral deformity. Herein, we report a case of SLS diagnosed based on imaging, genetic examination and autopsy findings. CASE PRESENTATION: From the 19th to 23rd weeks of gestation, the foetus presented with brachioesophagus, secondary intrathoracic stomach, intrathoracic spleen with poly-spleen malformation, spinal deformity and diaphragm dysplasia, and some abdominal organs were partly located in the thoracic cavity. After extensive counselling, the couple opted to terminate the pregnancy. Whole genome sequencing and autopsy were performed. Then, the foetus was diagnosed with SLS. DISCUSSION AND CONCLUSIONS: SLS is characterized by multiorgan deformities and is associated with poor prognosis. Multiorgan deformities can be detected on prenatal sonography using three-dimensional ultrasound technology.

Reference ranges of fetal heart function using a Modified Myocardial Performance Index: a prospective multicentre, cross-sectional study.

OBJECTIVES: The primary aim of this study was to establish the normal reference ranges of the fetal left ventricular (LV) Modified Myocardial Performance Index (Mod-MPI). A secondary aim was to evaluate the agreement between manual and automatic measurements for fetal Mod-MPI. DESIGN: A prospective, multicentre, cross-sectional study. PARTICIPANTS: Normal singleton pregnancies. METHODS: The LV functions of normal singleton pregnancies were assessed in nine centres covering eight provinces in China using unified ultrasound protocols and settings and standardised measurements by pulsed Doppler at 20-24, 28-32 and 34-38 weeks of gestation. The isovolumetric relaxation time (IRT), isovolumetric contraction time, ejection time (ET) and Mod-MPI were measured both automatically and manually. RESULTS: This cross-sectional study included 2081 fetuses, and there was a linear correlation between gestational age (GA) and Mod-MPI (0.416+0.001×GA (weeks), p<0.001, r2=0.013), IRT (36.201+0.162× GA (weeks), p<0.001, r2=0.021) and ET (171.418-0.078*GA (weeks), p<0.001, r2=0.002). This finding was verified using longitudinal data in a subgroup of 610 women. The agreement between the manual and automated measurements for Mod-MPI was good. CONCLUSIONS: We constructed normal reference values of fetal LV Mod-MPI. Automatic measurement can be considered for ease of measurement in view of the good agreement between the automatic and manual values.

Aortic dissection during pregnancy and postpartum.

BACKGROUND: Patients with aortic dissection during pregnancy and postpartum period exhibit a high mortality. At present, a complete overview of aortic dissection during pregnancy and postpartum period is lacking. ​Methods: This systematic review included 80 reports published from 2000 to 2020, comprising a total study population of 103 patients with aortic dissection. ​Results: We found that Stanford Type A aortic dissection was more common in prepartum cases, especially in the third trimester, while postpartum cases of aortic dissection were more common in Stanford Type B. The most common risk factor was connective tissue disease, with no other known risk factors. The mode of delivery had no significant effect on the type of postpartum aortic dissection. Reduced maternal and fetal mortality was observed when patients with Stanford Type A aortic dissection occurring after 28 gestational weeks underwent cesarean section followed by aortic replacement. Patients with Stanford Type B aortic dissection were treated mainly with medication and/or endovascular repair. ​Conclusion: Contemporary management of patients during pregnancy and within 12 weeks postpartum requires multidisciplinary cooperation and includes serial, noninvasive imaging, biomarker testing, and genetic risk profiling for aortopathy. Early diagnosis and accurate treatment are essential to reduce maternal and fetal mortality.

Evaluation of Hemodynamic Changes in Fetuses With Isolated Mild-to-Moderate Ventriculomegaly by Transabdominal Ultrasound.

OBJECTIVES: To investigate fetal hemodynamic alterations using transabdominal ultrasound in fetuses with isolated mild-to-moderate ventriculomegaly (VM). METHODS: Fetuses diagnosed with isolated mild-to-moderate VM by transabdominal ultrasound were evaluated for hemodynamic changes, including changes in fetal cardiac function, the umbilical artery, the ductus venosus, and the middle cerebral artery. The fetuses with isolated mild-to-moderate VM were divided into 2 groups, namely, before 32 weeks' gestation (20 weeks-31 weeks 6 days) and after 32 weeks' gestation (32-38 weeks), and matched to corresponding healthy control fetuses. RESULTS: The 53 fetuses with VM before 32 weeks had a longer mean isovolumetric relaxation time (IRT; mean ± SD, 42.9 ± 6.8 versus 40.4 ± 5.0 milliseconds; P < .05) and an apparently higher modified myocardial performance index 0.46 ± 0.06 versus 0.43 ± 0.05; P < .01) than the healthy control fetuses. The 43 fetuses with VM after 32 weeks had a significantly longer mean IRT (45.5 ± 6.7 versus 40.9 ± 7.2 milliseconds; P < .01) and a lower UA pulsatility index (0.81 ± 0.13 versus 0.89 ± 0.11; P < .01). The optimal cutoff levels for the IRT in the prediction of adverse perinatal outcomes were 40 and 43 milliseconds before and after 32 weeks, respectively (sensitivity, 100% versus 100%; specificity, 40.4% versus 50.0%; area under the curve, 0.601 versus 0.748; 95% confidence interval, 0.457-0.733 versus 0.590-0.869; P = .291 versus .005). CONCLUSIONS: Some fetuses with isolated mild-to-moderate VM may have impaired cardiac function, characterized by a higher modified myocardial performance index or longer IRT. This finding might be useful for improving fetal surveillance.

Assessment of fetal modified myocardial performance index in early-onset and late-onset fetal growth restriction.

AIM: To investigate the changes of modified myocardial performance index (Mod-MPI) in early-onset and late-onset fetal growth restriction (FGR) cases, and its association with adverse perinatal outcome. METHODS: This was a prospective study on 77 early-onset and 100 late-onset FGR cases. Hundred normal fetuses were matched as control groups for early-onset and late-onset FGR groups, respectively. Mod-MPI and vessel Doppler parameters including umbilical artery (UA), ductus venosus (DV), and middle cerebral artery (MCA) were measured. Perinatal outcomes were followed up. Mod-MPI of FGR cases were compared in normal Doppler, abnormal Doppler, and control groups. The association of Mod-MPI and perinatal outcome was investigated, and further efficacy of Mod-MPI predicting adverse outcome was studied. RESULTS: Compared with control groups, both abnormal and normal Doppler groups showed increased Mod-MPI in early-onset and late-onset FGR, respectively. Mod-MPI had no significant difference between abnormal and normal Doppler groups. Mod-MPI was associated with adverse outcome in early-onset FGR (OR = 3.307) and late-onset FGR (OR = 3.412). The sensitivity and specificity of Mod-MPI predicting adverse outcome were 60% and 80% when cutoff value was 0.47 in early-onset FGR. And they were 65% and 70% when cutoff value was 0.50 in late-onset FGR. CONCLUSION: Fetal growth restriction fetuses had increased Mod-MPI. Mod-MPI could be used to predict adverse perinatal outcome of FGR fetuses. Mod-MPI was an effective parameter to supplement vessels' Doppler parameters in monitoring FGR.

Next-generation sequencing identified genetic variations in families with fetal non-syndromic atrioventricular septal defects.

Atrioventricular septal defects (AVSDs) account for approximately 5% of all congenital heart disease (CHD). About half of AVSDs are diagnosed in cases with trisomy 21 (Down's syndrome, DS). However, many AVSDs occur sporadically and manifest as non-syndromic. The pathogenesis is complex and has not yet been fully elucidated. In the present study, we applied two advanced applications of next-generation sequencing (NGS) to explore the genetic variations in families with fetal non-syndromic AVSDs. Our study was mainly divided into two steps: (1) low-pass whole-genome sequencing (WGS) was used to detect the genome-wide copy number variations (CNVs) for included subjects; (2) whole-exome sequencing (WES) was used to detect the gene mutations for the subjects without AVSD-associated CNVs. A total of 17 heterozygous de novo CNVs and 19 heterozygous de novo gene mutations were selected, and 15 candidate genes were involved in these variations. Among these heterozygous de novo variations, most have potential pathogenicity for AVSDs, but the others require further investigation to confirm their pathogenicity. Our study not only shows the genetic diversity and the etiological complexity of AVSDs but also shows the rationality and practicability of this sequential genetic detection and analysis strategy.

Assessment of Fetal Myocardial Performance Index in Women with Placenta Previa.

BACKGROUND This study investigated whether fetuses of placenta previa pregnancies have cardiac dysfunction by use of a modified myocardial performance index (Mod-MPI). MATERIAL AND METHODS A prospective cross-sectional study was conducted including 178 fetuses at 28-40 weeks of gestation. Eighty-nine fetuses of mothers with placenta previa and without pregnancy complications were recruited (placenta previa group) and matched with 89 fetuses of mothers with normal pregnancies (control group). Fetal cardiac function parameters and perinatal outcomes as well as the Mod-MPI were compared between the 2 groups. RESULTS The median Mod-MPI was significantly increased in fetuses of mothers with placenta previa compared with controls (0.47±0.05 vs. 0.45±0.05; P<0.01). Among fetuses of mothers with or without placenta previa, the Mod-MPI was significantly higher in the incomplete placenta previa group compared with the complete placenta previa group and control group (P<0.01). An increased Mod-MPI in placenta previa pregnancies was independently associated with fetal cord pH <7.2 (odds ratio, 4.8; 95% confidence interval, 0.98-23.54; P=0.003). CONCLUSIONS There is impairment of fetal cardiac function in pregnancies with placenta previa. An increased MPI was independently associated with adverse perinatal outcomes to some extent in the placenta previa pregnancies.

Fluoxetine, an Antidepressant Drug, Inhibited Cigarette Smoke-Induced Pulmonary Inflammation and Apoptosis in Rats.

The present study was designed to evaluate the anti-inflammatory effect of fluoxetine (Flu) against cigarette smoke (CS)-induced chronic obstructive pulmonary disease (COPD) in rats. Forty male Sprague-Dawley (SD) rats were randomly assigned to five groups: control group, CS group, dexamethasone (2 mg/kg) group, and flu (2 mg/kg). H&E staining demonstrated that Flu inhibited CS-induced pathological injury. In addition, Flu could restore the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in serum. Flu also inhibited the levels of cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß). Furthermore, flu significantly inhibited the protein levels of TLR/NF-κB and apoptosis pathway in CS-induced rats. Our findings suggested that flu might effectively ameliorate the progression of COPD via inflammation and apoptosis pathway in rats.