Association between abnormal uterine artery pulsatility index and the risk of fetal congenital heart defects: a hospital-based cohort study.

To explore the associations between high uterine artery pulsatility index (UtA-PI) values and congenital heart disease (CHD) risk and whether they differed between singleton and multiple pregnancies. This hospital-based cohort study involving 52,047 pregnant women who underwent prenatal examinations from 2012 to 2016. Infants born to the included pregnant women were followed until 42 days after birth to identify those with CHDs. Generalized estimating equations were used to estimate the associations of high right UtA-PI (> 95th percentile) values with maternal preeclampsia and fetal CHDs. Logistic regression analyses were conducted using path analysis models to quantify the effect of high right UtA-PI values on fetal CHD risk. A total of 42,552 women and 43,470 infants (147 with CHDs) were included. Preeclampsia risk was associated with a high right UtA-PI in singleton-pregnant women (adjusted PR, 3.01; 95% CI 2.57-3.52). CHD risk was marginally associated with a high right UtA-PI in singleton-pregnant women (adjusted PR, 2.26, 95% CI 1.03-4.95). Considering only two factors, 96.0% of the fetal CHD risk was mediated by preeclampsia in singleton-pregnant women, while 93.8% of the risk was related to a high right UtA-PI in multiple-pregnant women. A high right UtA-PI was marginally associated with an increased fetal CHD risk in singleton-pregnant women and might play an important role in multiple-pregnant women. Further studies are warranted to confirm these findings given the high loss to follow-up rate.

Comparison of the left and right ventricular size and systolic function of low-risk fetuses in the third trimester: Which is more dominant?

Objective: To quantify fetal cardiovascular parameters utilizing fetal-specific 2D speckle tracking technique and to explore the differences in size and systolic function of the left and right ventricles in low-risk pregnancy. Methods: A prospective cohort study was performed in 453 low-risk single fetuses (28+0-39+6 weeks) to evaluate ventricular size [i.e., end-diastolic length (EDL), end-systolic length (ESL), end-diastolic diameter (ED), end-systolic diameter (ES), end-diastolic area, end-systolic area, end-diastolic volume (EDV), and end-systolic volume (ESV)] and systolic function [i.e., ejection fraction (EF), stroke volume (SV), cardiac output (CO), cardiac output per kilogram (CO/KG), and stroke volume per kilogram (SV/KG)]. Results: This study showed that (1) the reproducibility of the interobserver and intraobserver measurements was good to excellent (ICC 0.626-0.936); (2) with advancing gestation, fetal ventricular size and systolic function increased, whereas right ventricular (RV) EF decreased and left ventricular (LV) EF was not significantly changed; (3) LV length was longer than RV length in diastole (2.24 vs. 1.96 cm, P < 0.001) and systole (1.72 vs. 1.52 cm, P < 0.001); (4) LV ED-S1 and ES-S1 were shorter than the RV ED-S1 and ES-S1 (12.87 vs. 13.43 mm, P < 0.001; 5.09 vs. 5.61 mm, P < 0.001); (5) there were no differences between the LV and RV in EDA or EDV; (6) the mean EDV ratio of right-to-left ventricle was 1.076 (95% CI, 1.038-1.114), and the mean ESV ratio was 1.628 (95% CI, 1.555-1.701); (7) the EF, CO and SV of the LV were greater than the RV (EF: 62.69% vs. 46.09%, P < 0.001; CO: 167.85 vs. 128.69 ml, P < 0.001; SV: 1.18 vs. 0.88 ml, P < 0.001); (8) SV and CO increased with ED-S1 and EDL, but EF was not significantly changed. Conclusion: Low-risk fetal cardiovascular physiology is characterized by a larger RV volume (especially after 32 weeks) and greater LV outputs (EF, CO, SV, SV/KG and CO/KG).

High maternal blood lipid levels during early pregnancy are associated with increased risk of congenital heart disease in offspring.

INTRODUCTION: This study aimed to investigate whether maternal blood lipid levels during early pregnancy are associated with the occurrence of congenital heart disease (CHD) in their offspring. MATERIAL AND METHODS: In this single-center case-control study, mothers of offspring with CHD (n = 230) and without CHD (n = 381) were included. Maternal lipid levels were determined on fasting blood samples taken in the first trimester. Relevant demographic and clinical data were extracted from the medical records. Maternal lipid profile was compared between the two groups, and regression analysis was performed to evaluate the association between lipid profile and CHD risk in offspring. RESULTS: Compared with the control group, levels of triglyceride, apolipoprotein-A1, and apolipoprotein-B in early pregnancy were significantly higher in the CHD group. Multivariate analyses showed that triglyceride (odds ratio [OR] 2.46, 95% CI 1.62-3.73, p < 0.01), total/high-density lipoprotein cholesterol (OR 2.10, 95% CI 1.07-4.13, p = 0.03), and apolipoprotein-A1 (OR 2.73, 95% CI 1.16-6.40, p = 0.02) were positively associated with CHD risk in offspring. CONCLUSIONS: Elevated maternal lipid profile was associated with increased risk of CHD in offspring.

Abnormal placental perfusion and the risk of stillbirth: a hospital-based retrospective cohort study.

BACKGROUND: A lack of information on specific and interventional factors for stillbirth has made designing preventive strategies difficult, and the stillbirth rate has declined more slowly than the neonatal death rate. We compared the prevalence of stillbirth among the offspring of women with or without abnormal placental perfusion (APP). METHODS: We conducted a hospital-based retrospective cohort study involving women with a singleton pregnancy between 2012 and 2016 (N = 41,632). Multivariate analysis was performed to compare the prevalence of stillbirth in infants exposed to APP (defined as any abnormality in right or left uterine artery pulsatility index or resistance index [UtA-PI, -RI] [e.g., > 95th percentile] or presence of early diastolic notching) with that in those not exposed to APP. RESULTS: Stillbirths were more common among women with APP than among those with normal placental perfusion (stillbirth rate, 4.3 ‰ vs 0.9 ‰; odds ratio (OR), 4.2; 95% confidence interval (CI), 2.2 to 8.0). The association strengths were consistent across groups of infants exposed to APP that separately defined by abnormality in right or left UtA-PI or -RI (OR ranged from 3.2 to 5.3; all P ≤ 0.008). The associations were slightly stronger for the unexplained stillbirths. Most of the unexplained stillbirth risk was attributed to APP (59.0%), while a foetal sex disparity existed (94.5% for males and 58.0% for females). Women with normal placental perfusion and a male foetus had higher credibility (e.g., higher specificities) in excluding stillbirths than those with APP and a female foetus at any given false negative rate from 1 to 10% (93.4% ~ 94.1% vs. 12.3% ~ 14.0%). CONCLUSIONS: APP is associated with and accounts for most of the unexplained stillbirth risk. Different mechanisms exist between the sexes. The performance of screening for stillbirth may be improved by stratification according to sex and placental perfusion.

Association of abnormal placental perfusion with the risk of male hypospadias: a hospital-based retrospective cohort study.

BACKGROUND: The effect and extent of abnormal placental perfusion (APP) on the risk of male hypospadias are poorly understood. We compared the prevalence of male hypospadias in the offspring of women with APP and quantify the extent of the APP effect on the anomaly. METHODS: A hospital-based retrospective analysis of births from 2012 to 2016 was conducted in 2018. Women of singleton pregnancy and male infants born to them were included (N = 21,447). A multivariate analysis was performed to compare the prevalence of male hypospadias in infants exposed to APP with those that were not exposed to APP. RESULTS: Compared with the infants of women without APP, infants of women with APP showed an increased risk of male hypospadias (odds ratio, 2.40; 95% confidence interval, 1.09-5.29). The male hypospadias cumulative risk increased with the severity of APP. Infants exposed to severe APP had a significantly higher risk of male hypospadias than those without APP exposure (9.2 versus 1.7 per 1000 infants, P < 0.001). A path analysis indicated that 28.18-46.61% of the risk of hypospadias may be attributed to the effect of APP. CONCLUSIONS: Male hypospadias risk was associated with APP and increased with APP severity, as measured in the second trimester. APP had an important role in the development of the anomaly.

A Comparison of Prediction of Adverse Perinatal Outcomes between Hadlock and INTERGROWTH-21st Standards at the Third Trimester.

Little is known about the clinical value of the Hadlock and INTERGROWTH-21st EFW standards for predicting adverse perinatal outcomes (APOs) in the third trimester. The purpose of this study was to study the association between low estimated fetal weight percentile (EFWc) in the third trimester and the risk of APOs and compare predictions of APOs between Hadlock and INTERGROWTH-21st EFW standards. A prospective cohort of 690 singleton pregnancies with ultrasonography performed in the third trimester between March 2015 and March 2016 in China was conducted. EFW and the corresponding EFWc were measured using the Hadlock and INTERGROWTH-21st standards, respectively. Cox proportional hazard models were used to assess the relationship between low EFWc (i.e., <5 percentile, P5) and the risk of APOs. Compared with fetuses with ≥P5 of the EFWc, fetuses with

The impacts of maternal gestational diabetes mellitus (GDM) on fetal hearts.

OBJECTIVE: To evaluate the fetal cardiac function in gestational diabetes mellitus (GDM) pregnancies under different maternal glycemic controls. METHODS: Forty four GDM mothers received 78 fetal echocardiographic evaluations at three gestational periods (<28, 28-34 and >34 weeks) and were divided into poorly-(DM1) and well-(DM2) controlled groups according to their glycemic control at examination. Seventy uncomplicated mothers were selected as controls. Parameters of fetal cardiac anatomy and function were measured and analyzed. RESULTS: GDM fetuses' cardiac ventricular walls were thicker than controls', and the differences between DM1 and DM2 were not significant except for end-diastolic left ventricular walls. In both GDM groups, the aortic flow velocities increased earlier than pulmonary artery and DM1 fetuses changed earlier than DM2 ones. GDM fetuses' left atrial shortening fraction was smaller than the controls' in the period of ⩾34 weeks and negatively correlated with thicknesses of left ventricular walls and interventricular septum in DM1 fetuses (r=-0.438 and -0.506). The right ventricular diastolic function in DM1 and DM2 fetuses decreased after the period of 28-34 weeks and in the period of >34 weeks respectively. Tei index of both left and right ventricles increased in DM1 group after the period of <28 weeks and in DM2 group only in the period of ⩾34 weeks, with no significant differences between DM1 and DM2 groups in this period. CONCLUSION: Fetuses of GDM mothers showed cardiac function impairments. Good maternal glycemic control may delay the impairments, but cannot reduce the degree. Some cardiac changes in GDM fetuses were similar to those in pregestational diabetic pregnancies except for several parameters and their changing time.

[Evaluation of cardiac function in fetuses from pregnant women with abnormal blood glucose levels by brain natriuretic peptide in umbilical cord blood].

OBJECTIVE: To study the feasibility of umbilical cord brain natriuretic peptide (BNP) level measurement for the evaluation of perinatal cardiac function in fetuses from pregnant women with abnormal blood glucose levels and the influence of abnormal blood glucose on fetal cardiac function. METHODS: Twenty-four mothers with gestational diabetes mellitus (n=18) or gestational impaired glucose tolerance (n=6) (diabetic group) were classified into two subgroups according to blood glucose level before delivery: good (n=17) and poor (n=7) glucose control. They underwent fetal echocardiography in their late pregnant periods and fetal cardiac sizes and function were measured. Twenty-five normal pregnant mothers served as the control group. Umbilical cord blood BNP concentrations were measured at delivery. RESULTS: The umbilical cord blood BNP concentrations in the diabetic group were significantly higher than in the control group(114.0+/-39.0 pg/mL vs 80.6+/-13.7 pg/mL; p<0.01). The poor glucose control subgroup demonstrated higher umbilical cord blood BNP concentrations than the good glucose control subgroup (142.1+/-44.1 pg/mL vs 102.4+/-31.2 pg/mL; p<0.01). No difference was found between the gestational diabetes mellitus and the impaired glucose tolerance groups. The BNP concentration was positively correlated to the thicknesses of fetal left ventricular walls and the peak velocities of mitral A wave (r=0.715, 0.491 respectively, p<0.05), and negatively correlated to the mitral E/A ratio (r=-0.507, p<0.05). CONCLUSIONS: The fetuses of pregnant women with abnormal blood glucose levels have an increased BNP level in umbilical cord blood. Umbilical cord BNP level is related to maternal blood glucose control and the changes in fetal cardiac function. It may reflex the latent impairments of fetal cardiac function. A good glucose control may decrease the impact of abnormal maternal blood glucose on fetal hearts.

[Evaluation of the prenatal screening mode for fetal congenital heart diseases by ultrasound].

OBJECTIVE: To assess prenatal heart disease screening program by ultrasound. METHODS: A total of 11,544 second-trimester screening scans were performed before 24 weeks' gestation on 11,410 women between February 2004 and May 2007 in Obstetrics and Gynecology Hospital of Fudan University. Fetal heart screening was based on four-chamber and outflow tract views (left ventricular outflow + three vessel view). The sensitivity and specificity of different views were evaluated. Follow-up data of newborns was obtained. RESULTS: (1) Among 11,544 cases,48 cases of congenital heart disease (CHD) were diagnosed in utero. Six cases were false negative, and 2 cases were false positive. The incidence of CHD was 0.47% (54/11 544). (2) Thirty-three CHDs were detected based on the four-chamber view, including 18 ventricular septal defect (9 with conotruncal anomalies), 6 anomalous atrioventricle valve, 9 disproportion of left/right ventricle. The sensitivity of the four-chamber view alone was 61.11% (33/54), and the specificity was 99.98% (11 488/11 490). Fifteen CHDs were detected based on the left ventricular outflow and three vessel views, including 1 pulmonary atresia, 3 pulmonary valve stenosis, 2 transposition of the great arteries (TGA), 1 pulmonary stenosis with TGA, 6 tetralogy of Fallot, and 2 pulmonary stenosis. The sensitivity of the combination of the four-chamber and outflow tract views was 88.89% (48/54), and the specificity was 99.98% (11 488/11 490). (3) Of 48 CHDs, 11 cases were accompanied by other malformations. Eleven cases were performed amniocentesis, among whom 5 cases were trisomy 21. CONCLUSION: The screening program based on four-chamber and outflow tract views shows good sensitivity and excellent specificity. Our prenatal heart screening program is clinically feasible.