ROR2 deficit may induce the tetralogy of Fallot via down-regulating of ß-catenin/SOX3/HSPA6 in vitro and in vivo.

Tetralogy of Fallot (TOF) is the highly conventional appearance of cyanotic congenital heart disease. Our study aimed to assess the involvement of receptor tyrosine kinase-like orphan receptor 2 (ROR2) in TOF and elucidate the specific mechanism. Upon investigation of human tissue samples, we observed a decrease in ROR2 expression in TOF patients compared to healthy control individuals. Transcriptome analysis revealed diminished ROR2 expression in TOF pathological samples relative to normal tissues. Of the 2246 genes that exhibited altered expression, 886 were upregulated, while 1360 were down-regulated. KEGG analysis and GO analysis of the differentially expressed genes indicated that these genes were significantly enriched in the Wnt signalling pathway, apoptosis and cardiac development function. Importantly, ROR2 was the only gene shared among the three pathways. Furthermore, interference with ROR2 promotes apoptosis and curtails cell proliferation in vitro. The knockdown of the ROR2 gene in AC16 cells resulted in a significant decrease in Edu-positive cells. Flow cytometry studies indicated an increase in the percentage of cells in the S phase. In contrast, the G2/M cell cycle transition was blocked in the ROR2-knockdown group, leading to a significant increase in apoptosis. Moreover, the CCK-8 cell viability assay demonstrated a reduced proliferation in the ROR2-knockdown group. Furthermore, both in vivo and in vitro data indicated that the expression of HSPA6 (Recombinant Heat Shock 70 kDa Protein6), an essential gene enriched in cardiac tissue and associated with apoptosis, was down-regulated following ROR2 knockdown mediated by the ß-catenin/SOX3 signalling pathway. In conclusion, low expression of ROR2 plays a crucial role in the occurrence and development of TOF, which may be related to the downregulation of HSPA6 through the ß-catenin/SOX3 signalling pathway.

Application of Foley balloon catheter in palliative surgery for pulmonary atresia with an intact ventricular septem, with additional cases of pulmonary atresia with ventricular septal defect and tetralogy of Fallot.

BACKGROUND: Pulmonary atresia and tetralogy of Fallot can require palliative surgery in the neonatal period due to severe hypoxia; however, limitations of established techniques include high failure rate and need for cardiopulmonary bypass. Herein, right ventricular outflow tract reconstruction on a beating heart using a Foley balloon catheter is described. METHODS: A retrospective review of patients who underwent right ventricular outflow tract reconstruction on a beating heart using a Foley balloon catheter at our institution between September 2018 and March 2022 was completed. During the procedure, a Foley balloon catheter was used to occlude the blood from the right ventricular inflow tract. RESULTS: Eight patients with pulmonary atresia and intact ventricular septum underwent an off-pump right ventricular outflow tract reconstruction. One patient with pulmonary atresia and ventricular septal defect, and two patients with tetralogy of Fallot underwent an on-pump right ventricular outflow tract reconstruction on a beating heart. The procedures were successful in all patients. Patent ductus arteriosus ligation without modified Blalock-Taussig shunt placement was performed in three patients with pulmonary atresia with intact ventricular septum and two patients with tetralogy of Fallot, ductus arteriosus was left open in four patients with pulmonary atresia with intact ventricular septum. All patients remained clinically well without serious complications. CONCLUSIONS: Right ventricular outflow tract reconstruction on a beating heart using a Foley balloon catheter for pulmonary atresia and tetralogy of Fallot is a feasible alternative to catheter-based interventions or traditional surgical treatment, especially in patients with muscular infundibular stenosis or hypoplastic pulmonary annulus. Further studies with more cases are needed to verify feasibility and superiority of this approach.

[Integrated management during the perinatal period for total anomalous pulmonary venous connection]. / å®Œå ¨æ€§è‚ºé™è„‰å¼‚ä½è¿žæŽ¥çš„å›´ç”ŸæœŸä¸€ä½“åŒ–ç®¡ç†.

OBJECTIVES: To evaluate the clinical effectiveness of integrated management during the perinatal period for fetuses diagnosed with total anomalous pulmonary venous connection (TAPVC) by prenatal echocardiography. METHODS: Clinical data of 64 cases of TAPVC fetuses diagnosed by prenatal echocardiography and managed with integrated perinatal care in Qingdao Women and Children's Hospital from January 2017 to December 2021 were retrospectively analyzed. Integrated perinatal care included multidisciplinary collaboration among obstetrics, fetal medicine, ultrasound, pediatric cardiology, pediatric anesthesia, and neonatology. RESULTS: Among the 64 TAPVC fetuses, there were 29 cases of supracardiac type, 27 cases of intracardiac type, 2 cases of infracardiac type, and 6 cases of mixed type. Chromosomal analysis was performed in 42 cases, and no obvious abnormalities were found. Among the 64 TAPVC fetuses, 37 were induced labor, and 27 were followed up until term birth. Among the 27 TAPVC cases, 2 cases accepted palliative care, 2 cases were referred to another hospital for treatment and lost to follow-up, while the remaining 23 cases underwent primary repair surgery. One case died within 6 months after the operation due to low cardiac output syndrome, while the other 22 cases were followed up for (2.1±0.3) years with good outcomes (2 cases underwent a second surgery within 1 year after the first operation due to anastomotic stenosis or pulmonary vein stenosis). CONCLUSIONS: TAPVC fetuses can achieve good outcomes with integrated management during the perinatal period.

Identification of novel rare copy number variants associated with sporadic tetralogy of Fallot and clinical implications.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Highly penetrant copy number variants (CNVs) and genes related to the etiology of TOF likely exist with differences among populations. We aimed to identify CNV contributions to sporadic TOF cases in Han Chinese. Genomic DNA was extracted from peripheral blood in 605 subjects (303 sporadic TOF and 302 unaffected Han Chinese [Control] from cardiac centers in China) and analyzed by genome-wide association study (GWAS). The GWAS results were compared with existing Database of Genetic Variants. These CNVs were further validated by qPCR. Bioinformatics analyses were performed with protein-protein interaction (PPI) network and KEGG pathway enrichment. Across all chromosomes 119 novel "TOF-specific CNVs" were identified with prevalence of CNVs of 21.5% in chromosomes 1-20 and 37.0% including Chr21/22. In chromosomes 1-20, CNVs on 11q25 (encompasses genes ACAD8, B3GAT1, GLB1L2, GLB1L3, IGSF9B, JAM3, LOC100128239, LOC283177, MIR4697, MIR4697HG, NCAPD3, OPCML, SPATA19, THYN1, and VPS26B) and 14q32.33 (encompasses genes THYN1, OPCML, and NCAPD3) encompass genes most likely to be associated with TOF. Specific CNVs found on the chromosome 21 (6.3%) and 22(11.9%) were also identified in details. PPI network analysis identified the genes covering the specific CNVs related to TOF and the signaling pathways. This study for first time identified novel TOF-specific CNVs in the Han Chinese with higher frequency than in Caucasians and with 11q25 and 14q32.33 not reported in TOF of Caucasians. These novel CNVs identify new candidate genes for TOF and provide new insights into genetic basis of TOF.

High-Intensity Focused Ultrasound in Interventricular Septal Myocardial Ablation.

High-intensity focused ultrasound (HIFU) can cause necrotic damage in deep tissues through thermal ablation and cavitation, without significant damage to the surrounding tissues. High blood perfusion of heart affects the energy deposition. This study aimed to evaluate the effect of cooling of coronary blood flow for HIFU ablation.Continuous and pulsed HIFU (2000 J) at duty cycles of 100% and 25% were examined for their capacity to ablate the perfused porcine heart tissue in vitro. After ablation, grayscale changes and pathological features were observed or measured, and the area and volume of tissue necrosis were calculated.The cardiomyocytes in the lesions underwent necrosis with a clear boundary. The endocardial surface was intact without necrosis. The three-dimensional morphology of the lesions appeared approximately as ellipsoids. With the increase in perfusion speed, the necrotic volume in the target area was gradually reduced.HIFU has the potential to become a new minimally invasive surgery for ventricular septal myocardial ablation. Reduction of coronary blood flow can improve the ablation effect.

Differential effect of pre-pregnancy low BMI on fetal macrosomia: a population-based cohort study.

BACKGROUND: The differential effect of pre-pregnancy low BMI on macrosomia has not been fully addressed. Herein, we conducted a city-wide population-based cohort study to illuminate the association between pre-pregnancy low BMI and macrosomia, stratifying by maternal age, parity, and GDM status. METHODS: All pregnant women who paid their first prenatal visit to the hospital in Qingdao during August 1, 2018, to June 30, 2020, were recruited to this study. The interactive effect of maternal age and pre-pregnancy low BMI on macrosomia was evaluated using logistic regression models, followed by strata-specific analyses. RESULTS: A total of 105,768 mother-child pairs were included, and the proportion of fetal macrosomia was 11.66%. The interactive effect of maternal pre-pregnancy BMI and age was statistically significant on macrosomia irrespective of parity (nullipara: Padjusted=0.0265; multipara: Padjusted=0.0356). The protective effect of low BMI on macrosomia was most prominent among nullipara aged 35 years and above (aOR=0.16, 95% CI 0.05-0.49) and multipara aged 25 years and below (aOR=0.17, 95% CI 0.05-0.55). In nullipara without GDM, the risk estimates gradually declined with increasing conception age (20-to-24 years: aOR=0.64, 95% CI 0.51-0.80; 25-to-29 years: aOR=0.43 95% CI 0.36-0.52; 30-to-34 years: aOR=0.40 95% CI 0.29-0.53; and ≥35 years: aOR=0.19, 95% CI 0.06-0.60). A similar pattern could also be observed in nullipara with GDM, where the aOR for low BMI on macrosomia decreased from 0.54 (95% CI 0.32-0.93) in pregnant women aged 25-29 years to 0.30 (95% CI 0.12-0.75) among those aged 30-34 years. However, younger multiparous mothers, especially those aged 25 years and below without GDM (aOR=0.21, 95% CI 0.06-0.68), were more benefited from a lower BMI against the development of macrosomia. CONCLUSIONS: Maternal low BMI is inversely associated with macrosomia irrespective of maternal age and parity. The impact of pre-pregnancy low BMI on macrosomia varied by maternal age and parity. The protective effect of a lower maternal BMI against fetal macrosomia was more prominent in nulliparous mothers aged 35 years and above, whereas multiparous mothers younger than 25 years of age were more benefited.

Incidence and risk factors of congenital heart disease in Qingdao: a prospective cohort study.

BACKGROUND: Many studies have been conducted to assess the incidence of congenital heart disease (CHD). However, results were greatly inconsistent among these studies with a broad range of findings. METHODS: A prospective census-based cohort study was conducted in Qingdao, China, from August 1, 2018 to April 30, 2019. All of the local registered pregnant women were continuously investigated and followed from 15 to 20 weeks of gestation to delivery, tracking the CHD cases in both the fetal and neonatal stages. A logistic regression model was applied to assess the association between CHD and possible risk factors. RESULTS: The positive rate of prenatal CHD screening was 14.36 per 1000 fetuses and the incidence of CHD was 9.38 per 1000 live births. Results from logistic regression indicated that, living in the countryside (odds ratio, (OR): 0.771; 95% confidence interval, (CI): 0.628-0.946) and having a childbearing history (OR: 0.802; 95%CI: 0.676-0.951) were negatively associated with CHD. However, twin pregnancy (OR: 1.957, 95% CI: 1.245-3.076), illness in the first trimester (OR: 1.306; 95% CI: 1.048-1.628), a family history of CHD (OR: 7.156; 95% CI: 3.293-15.552), and having a child with a birth defect (OR: 2.086; 95% CI: 1.167-3.731) were positively associated with CHD. CONCLUSION: CHD is a serious health problem in Qingdao. The CHD incidence found in this study was similar to existing research. The positive rate of prenatal CHD screening was higher than the incidence of neonatal CHD. Moreover, CHD risk factors were identified in our study, and our findings may have great implications for formation CHD intervention strategies.

A simple method to remove a remnant sewing needle from the posterior pericardial cavity without cardiac arrest.

We reported a case of removing a remnant sewing needle without cardiac arrest from the posterior pericardial cavity after open-heart surgery for a 17-year-old male patient with atrial septal defect.

Treatment of Perimembranous Ventricular Septal Defect in Children Weighing Less than 15 kg: Minimally Invasive Periventricular Device Occlusion versus Right Subaxillary Small Incision Surgical Repair.

BACKGROUND: To compare the treatment outcomes between minimally invasive periventricular device occlusion (MIPDO) and right subaxillary incision surgical repair (RSISR) on perimembranous ventricular septal defect (PmVSD) in children weighing less than 15 kg. METHODS: From January 2010 to January 2013, 538 infants (age < 3 years, weight < 15 kg) with PmVSD were randomly divided into two groups according to different treatment methods. Group 1 (265 cases) had periventricular device occlusion through a lower partial median sternotomy under transesophageal echocardiography (TEE); group 2 (265 cases) underwent surgical repair on cardiopulmonary bypass (CPB) through a right subaxillary incision. A prospective randomized controlled study was performed regarding success rate, operation time, volume of blood loss and transfusion, length of intubation and intensive care unit (ICU) stay, complications, expenses, and follow-up results. RESULTS: All patients had effective treatment with no death or serious life-threatening complications. In group 1, 255 cases (96.23%) underwent successful periventricular device occlusion. The remaining 10 cases (3.77%) were successfully converted to conventional operation. Different arrhythmias arose in 30 cases (11.76%), trivial residual shunt (RS) in 18 cases (7.06%), and new trivial tricuspid regurgitation (TR) in 29 cases (11.37%). In group 2, all patients (100%) underwent successful surgical repair. Different arrhythmias occurred in 116 cases (43.77%), trivial RS in 16 cases (6.04%), new trivial TR in 11 cases (4.15%), and heart dysfunction in 17 patients (6.42%). All patients were followed for more than 12 months. The final treatment effects were similar in both groups, but group 1 was significantly superior to group 2 regarding operation time, volume of blood loss, length of intubation and ICU stay, hospitalizations, and costs (all p < 0.05). TR incidence was higher in group 1 (p < 0.05), and that of right bundle branch block was higher in group 2 (p < 0.05). The incision was longer in group 2, but in a less exposed location. CPB was not needed in group 1, but anticoagulants were required for 3 to 6 months. CONCLUSION: Both RSISR and MIPDO are effective treatment methods for PmVSD. Though having some limitations, MIPDO not only minimized the surgical trauma to patients but also ensured safety to the maximum extent. However, patient selection is vital. For selected patients, especially those with moderate PmVSDs with obvious clinical symptoms and no valve regurgitation, it seems an ideal approach.

Transcatheter Treatment of Large Aortopulmonary Window: A Case Report.

INTRODUCTION: Aortopulmonary window (APW), a large aortopulmonary septal defect (APSD), is a serious and rare defect within congenital heart diseases. CASE REPORT: In this study, we reported an APW case with severe pulmonary arterial hypertension. This patient was successfully treated by transcatheter closure with a muscular ventricular septal defect (VSD) occluder. CONCLUSION: We had a successful experience with transcatheter closure of a large APW using a muscular VSD occluder. There was no residual shunt or complications during the 6-month follow-up.

Progress of biodegradable polymer application in cardiac occluders.

Cardiac septal defect is the most prevalent congenital heart disease and is typically treated with open-heart surgery under cardiopulmonary bypass. Since the 1990s, with the advancement of interventional techniques and minimally invasive transthoracic closure techniques, cardiac occluder implantation represented by the Amplazter products has been the preferred treatment option. Currently, most occlusion devices used in clinical settings are primarily composed of Nitinol as the skeleton. Nevertheless, long-term follow-up studies have revealed various complications related to metal skeletons, including hemolysis, thrombus, metal allergy, cardiac erosion, and even severe atrioventricular block. Thus, occlusion devices made of biodegradable materials have become the focus of research. Over the past two decades, several bioabsorbable cardiac occluders for ventricular septal defect and atrial septal defect have been designed and trialed on animals or humans. This review summarizes the research progress of bioabsorbable cardiac occluders, the advantages and disadvantages of different biodegradable polymers used to fabricate occluders, and discusses future research directions concerning the structures and materials of bioabsorbable cardiac occluders.

Prenatal Diagnosis of Congenital Heart Disease and Voluntary Termination of Pregnancy: A Population-Based Study in Qingdao, China.

Objective: The outcomes of fetuses with isolated congenital heart disease (CHD) diagnosed prenatally have not been investigated in a population-based study in China. This population-based study aimed to evaluate the rate of voluntary termination of pregnancy after the prenatal diagnosis of isolated CHD in Qingdao, China. Methods: This was a population-based retrospective study in which data were collected from all pregnant women in Qingdao (eastern China) from August 2018 to July 2020; fetal data, maternal data and data on pregnancy outcomes were extracted from medical records regarding prenatal diagnosis of CHD. The inclusion criteria were as follows: pregnant women or their husbands who had a household registration in Qingdao and who underwent regular prenatal screening in Qingdao. The exclusion criterion was the failure to sign an informed consent form. Counseling for all parents of fetuses with CHD was provided by a multidisciplinary team of experienced pediatric cardiologists, obstetricians, geneticists, etc. According to the type and severity of CHD, the pregnancy termination rate was analyzed. Results: Among the 126,843 pregnant women, 1299 fetuses with a prenatal diagnosis of CHD were included in the study. Among the included fetuses, 1075 were diagnosed with isolated CHD, and the overall pregnancy termination rate was 22.8%. Termination rates varied according to the complexity of CHD (low complexity vs moderate complexity, P=0.000; low complexity vs high complexity, P=0.000; moderate complexity vs high complexity, P=0.000), with rates of 6.0% for low complexity, 54.2% for moderate complexity, and 99.1% for high complexity. The decision to terminate the pregnancy in cases of isolated CHD was unrelated to maternal age (P=0.091) but was related to gestational age (p=0.000). Conclusion: In Qingdao, 99.1% of parents whose fetuses were diagnosed with isolated high-complexity CHD chose to voluntarily terminate the pregnancy. The pregnancy termination rate increased with increasing complexity of prenatally diagnosed CHD.

Windows of sensitivity for risk of adverse birth outcomes related to gestational PM2.5 exposure: Evidence from a natural experiment.

While numerous studies have associated maternal exposure to PM2.5 with adverse birth outcomes, findings remain inconsistent and difficult to generalize. We aimed to investigate the causal relationship and window of sensitivity between gestational exposure to PM2.5 and birth outcomes. We leveraged high-resolution satellite data to quantify gestational PM2.5 exposure at the individual level, along with a combined model to determine daily relative risks (RRs) of birth outcomes in COVID-19 prelockdown and lockdown groups. RRs between the two groups were further compared using a longitudinal pre-post non-experimental design to identify sensitivity windows of adverse birth outcomes. A total of 73,781 pregnant women from the COVID-19 prelockdown group and 6267 pregnant women from the lockdown group were included for analysis. The daily mean PM2.5 concentrations in the lockdown group decreased by 21.7% compared to the prelockdown group. During the first trimester, every 10 µg/m3 increase in PM2.5 significantly increased the risk of congenital abnormalities of major organs such as the cardiovascular system, gastrointestinal tract, nervous system, urinary system, and respiratory system. Moreover, gestational exposure to PM2.5 during the first trimester was associated with higher risks of premature delivery and term low birth weight. While PM2.5 exposure during the second trimester was positively correlated with macrosomia. Gestational exposure to PM2.5 is associated with increased risks of various adverse birth outcomes with specific sensitive windows. We demonstrated that gestational exposure to PM2.5 increased risks of various adverse birth outcomes with specific window of sensitivity through the natural experiment design. Our findings underscore the urgent need for policies and initiatives targeting PM2.5 reduction, especially during critical periods of pregnancy.

Total cavopulmonary direct anastomosis in the beating heart without prosthetic material: preliminary experience with modified extracardiac fontan procedure.

AIM: To describe modified extracardiac Fontan procedure characterized with total cavopulmonary direct anastomosis in the beating heart without using prosthetic material in seven patients and summarize the clinical experiences and follow-up results. METHODS: From April 2007 to April 2011, seven patients with complex cardiac anomalies underwent this operation. The main pulmonary artery (MPA) was transected at the base of the pulmonary valve and the pulmonary annulus was oversewn. Then the inferior vena cava (ICV) was transected at the junction with the atrium. The MPA was brought to the side of the ICV and anastomosed in an end-to-end fashion. The superior vena cava (SVC) was transected at its entrance into the right atrium and was anastomosed to the right pulmonary artery. Five patients received transcatheter device closure of the fenestration with either a small atrial septal defect or ventricular septal defect occluder. RESULTS: All patients were in sinus rhythm and extubated on the first postoperative day. Immediate postoperative arterial oxygen saturation was 95% (93% to 96%). During the follow-up period from 17 to 65 months (median 48 months), there were no deaths and reoperations. Arterial oxygen saturation ranged from 88% to 92% on room air. The fenestration was closed in five patients postoperatively and the arterial oxygen saturation rose to 95%. CONCLUSION: Total cavopulmonary direct anastomosis in the beating heart without the use of prosthetic material provides growth potential, and avoids the need for anticoagulation. Longer follow-up will be necessary to evaluate this modification.

Giant right atrium in a child with dilated cardiomyopathy: A case report.

Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure in children with diverse clinical characteristics. To date, DCM with a giant atrium as the first manifestation is rare and has not been reported in previous literature. We report a case of a male infant born with a significantly enlarged right atrium. Due to worsened clinical symptoms and the risk of arrhythmias and thrombosis, we performed the surgical reduction of the right atrium. Unfortunately, DCM and a progressive re-enlargement of the right atrium appeared during midterm follow-up. The mother's echocardiogram also suggested DCM, and the patient was eventually considered for a diagnosis of familial DCM. This case may expand the clinical spectrum of DCM and reminds us of the importance of good follow-up of children with idiopathic dilatation of the right atrium.

Sutureless technique combined with vertical vein incision and pulmonary veins unroofed for correction of infracardiac total anomalous pulmonary venous connection.

Objective: We report a surgical method (sutureless technique), combined with vertical vein incision and pulmonary veins unroofed (semisutureless technique), to correct infracardiac total anomalous pulmonary venous connection (TAPVC). Materials and methods: The clinical characteristics of 21 patients, who were diagnosed with infracardiac TAPVS between February 2017 and March 2022, were retrospectively analyzed. These patients were divided into three groups according to different surgical methods: conventional surgery group, sutureless technique group, and semisutureless technique group. The conventional surgery group enrolled five patients with a median age of 16 days (interquartile range, 9-27 days) and a median weight of 3.25 kg (interquartile range, 3.1-3.42 kg). In this group, no preoperative pulmonary vein obstruction (PVO), preoperative ventilator support, or emergency surgery were reported. The sutureless technique group enrolled seven patients with a median age of 12 days (interquartile range, 5-16 days) and a median weight of 3.04 kg (interquartile range, 2.76-3.20 kg). In this group, two patients with preoperative PVO, four patients with preoperative ventilator support, and seven patients requiring emergency operation were found. The semisutureless technique group enrolled nine patients with a median age of 14 days (interquartile range, 7-24 days) and a median weight of 3.22 kg (interquartile range, 3.15-3.50 kg). In this group, four patients with preoperative PVO, two patients with preoperative ventilator support, and seven patients requiring emergency operation were noted. Results: In the conventional surgery group, two patients with postoperative supraventricular tachycardia, one patient with postoperative low cardiac output syndrome, one patient with PVO, and no case of postoperative death were reported. In the sutureless technique group, two patients with postoperative low cardiac output syndrome, one patient with postoperative supraventricular tachycardia, one patient with postoperative PVO, and no postoperative deaths were determined. In the semisutureless technique group, three patients had low cardiac output syndrome, two patients had supraventricular tachycardia after the operation, and one patient, who had been admitted to the hospital after cardiopulmonary resuscitation in the emergency room, died early after the operation. No case of death or PVO was noted after the operation. Conclusion: The semisutureless technique has positive effects. This surgery method can enlarge the anastomotic stoma, increase the volume of the left atrium, reduce the tension of the anastomotic stoma, fix the pulmonary vein to avoid distortion, and prevent postoperative hemorrhage.

Does recurrent gestational diabetes mellitus increase the risk of preterm birth? A population-based cohort study.

AIMS: To investigate whether recurrent gestational diabetes mellitus (GDM) is associated with an increased risk of preterm birth. METHODS: We conducted a prospective population-based cohort study covering all live singleton births born to nulliparous and multiparous mothers aged 20 years and older in Qingdao, from 2018 to 2020 (n = 105,528). Preterm birth (<37 gestational weeks) was classified into moderate preterm birth (32-36 weeks of gestation) and very preterm birth (<32 weeks). Logistic regression analysis was performed to estimate the risk and severity of prematurity in relation to parity among mothers with previous GDM, current GDM, and recurrent GDM (previous and current GDM), using mothers without GDM as the reference group. Z-test and ratio of odds ratios (ROR) were used to determine subgroup differences. RESULTS: Maternal GDM increased the risk of preterm birth in both nullipara (ORadj = 1.28, 95 %CI: 1.14-1.45) and multipara (ORadj = 1.26, 95 %CI: 1.14-1.40). However, the risk of premature delivery in multiparous mothers with recurrent GDM and those with current GDM did not differ significantly, with a ROR of 0.89 (95 %CI: 0.71-1.12). The risk of recurrent GDM on preterm birth was most pronounced among multiparous mothers with pre-pregnancy BMI above 30 kg/m2 (ORadj = 2.18, 95 %CI: 1.25-3.82) as compared with those with current GDM alone (ROR = 2.20, 95 %CI: 1.07-4.52). The risk of GDM for moderate preterm birth was similar to that of overall preterm birth. In contrast, GDM was not associated with very preterm birth irrespective of parity (all P values > 0.05). CONCLUSIONS: Maternal GDM increased the risk of preterm birth in nullipara and multipara, whereas recurrent GDM was not associated with a further increase in the risk of prematurity in multiparous mothers. Maternal GDM did not contribute to very preterm birth irrespective of parity. Our findings can be useful for facilitating more targeted preventive strategies for adverse pregnancy outcomes.