Risk of major congenital heart disease in pregestational maternal diabetes is modified by hemoglobin A1c.

OBJECTIVES: The association between pregestational diabetes mellitus (PDM) and risk of congenital heart disease (CHD) is well recognized; however, the importance of glycemic control and other coexisting risk factors during pregnancy is less clear. We sought to determine the relative risk (RR) of major CHD (mCHD) among offspring from pregnancies complicated by PDM and the effect of first-trimester glycemic control on mCHD risk. METHODS: We determined the incidence of mCHD (requiring surgery within 1 year of birth or resulting in pregnancy termination or fetal demise) among registered births in Alberta, Canada. Linkage of diabetes status, maximum hemoglobin A1c (HbA1c) at < 16 weeks' gestation and other covariates was performed using data from the Alberta Perinatal Health Program registry. Risk of mCHD according to HbA1c was estimated as an adjusted RR (aRR), calculated using log-binomial modeling. RESULTS: Of 1412 cases of mCHD in 594 773 (2.37/1000) births in the study period, mCHD was present in 48/7497 with PDM (6.4/1000; RR, 2.8 (95% CI, 2.1-3.7); P < 0.0001). In the entire cohort, increased maternal age (aRR, 1.03 (95% CI, 1.02-1.04); P < 0.0001) and multiple gestation (aRR, 1.37 (95% CI, 1.1-1.8); P = 0.02) were also associated with mCHD risk, whereas maternal prepregnancy weight > 91 kg was not. The stratified risk for mCHD associated with HbA1c ≤ 6.1%, > 6.1-8.0% and > 8.0% was 4.2/1000, 6.8/1000 and 17.1/1000 PDM/gestational diabetes mellitus births, respectively; the aRR of mCHD associated with PDM and HbA1c > 8.0% was 8.5 (95% CI, 5.0-14.4) compared to those without diabetes and 5.5 (95% CI, 1.6-19.4) compared to PDM with normal HbA1c (≤ 6.1%). CONCLUSIONS: PDM is associated with a RR of 2.8 for mCHD, increasing to 8.5 in those with HbA1c > 8%. These data should facilitate refinement of referral indications for high-risk pregnancy screening. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Clinical presentation, genetic etiology and outcome associated with fetal cardiomyopathy: comparison of two eras.

OBJECTIVE: To assess the rate and type of genetic diagnosis and clinical outcome of cases of fetal cardiomyopathy (CM) during two eras, in order to examine the impact of advanced genetic testing and improved perinatal management strategies. METHODS: All diagnoses of fetal CM in Alberta, Canada, encountered between 2003 and 2019, were reviewed retrospectively. Genetic, cardiac and non-cardiac diagnoses and clinical outcome were documented. Cases with CM secondary to extracardiac pathology and maternal conditions were excluded. Cases diagnosed in the earlier era of the study period (2003-2012) were compared with those diagnosed in the later era (2013-2019). RESULTS: Thirty-eight cases of fetal CM met the inclusion criteria. Median gestational age (GA) at diagnosis was 22.8 (range, 13.4-37.4) weeks. Associated structural heart disease was present in 39% (15/38) of cases and 24% (9/38) had arrhythmia. Hydrops was identified in 29% (11/38) of cases at presentation, and a further 18% (7/38) developed hydrops later in gestation. Twenty-six percent (10/38) of cases underwent termination of pregnancy and 24% (9/38) had intrauterine death. Of liveborn cases, neonatal death occurred in 16% (3/19), late death occurred in 21% (4/19) and 63% (12/19) were alive at the last follow-up. Excluding cases that had termination of pregnancy and those with a liveborn infant who received planned palliative care, the rate of neonatal survival was higher in the later compared with the earlier era (69% (11/16) vs 45% (5/11)), although the difference was not statistically significant (P = 0.26). A genetic etiology was confirmed in 39% (15/38) of cases and strongly suspected in 24% (9/38). A significantly higher proportion of cases had a confirmed or strongly suspected genetic etiology in the later era compared with in the earlier era (76% (19/25) vs 38% (5/13); P = 0.04). CONCLUSIONS: In the recent era, a higher proportion of fetal CM cases had a confirmed or strongly suspected genetic etiology than reported previously. Based on comparison with older series, modern perinatal management strategies may not have a significant impact on neonatal survival in cases of fetal CM; however, a larger study would be better powered to detect more subtle differences. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal features of ductus arteriosus-related branch pulmonary stenosis in fetal pulmonary atresia.

OBJECTIVE: Ductus arteriosus (DA)-related branch pulmonary stenosis (PS), due to ductal tissue migration into the proximal pulmonary artery (PA) ipsilateral to the DA, is common in newborns with pulmonary atresia (PAtr) and contributes significantly to their mortality and morbidity. We sought to define fetal echocardiographic predictors of DA-PS in PAtr. METHODS: This was a study of all neonates diagnosed prenatally with PAtr and a DA-dependent pulmonary circulation, with a DA that joined the underbelly of the arch, who had undergone surgical or catheter intervention in our hospital between 2009 and 2018. The postnatal echocardiograms and clinical records were reviewed to confirm the presence or absence of DA-PS based on the need for angioplasty at initial intervention and/or development of proximal PA stenosis post intervention. Fetal echocardiograms were examined for the features of DA-PS. RESULTS: Of 53 fetuses with PAtr, 34 (64%) had analyzable images, including 20/34 (59%) with and 14/34 (41%) without DA-PS. An inability to visualize the branch PAs in the same plane, largely associated with abnormal DA insertion into the ipsilateral PA (85% of cases), had sensitivity, specificity and positive (PPV) and negative (NPV) predictive values of 75%, 100%, 100% and 74%, respectively, for the prediction of postnatal DA-PS. The mean branch PA posterior bifurcation angle was more obtuse in cases with DA-PS compared to cases without DA-PS (117° ± 17° vs 79° ± 17°, P < 0.001), and an angle of > 100°, the preoperative cut-off observed previously in affected newborns, had a sensitivity, specificity, PPV and NPV of 88%, 79%, 82% and 85%, respectively. The receiver-operating-characteristics curve revealed an angle of ≥ 105° to have a sensitivity and specificity of 88% and 93%, respectively, for prenatal prediction of DA-PS. The presence of one or both features (inability to image in the same plane and the posterior bifurcation angle of ≥ 105°) had a sensitivity, specificity, PPV and NPV of 100%, 93%, 95% and 100%, respectively. CONCLUSION: An inability to visualize the branch PAs in the same plane, associated with abnormal insertion of the DA in most cases, and/or the presence of a posterior PA bifurcation angle of ≥ 105° are predictive features of postnatal DA-PS in fetuses with PAtr. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Changes in fetal cardiac axis between 8 and 15 weeks' gestation.

OBJECTIVES: To document changes in the normal embryonic/fetal cardiac axis in the late first and early second trimesters of pregnancy. METHODS: Images from 188 fetal echocardiograms performed prospectively between 8 and 15 weeks' gestation in 166 healthy pregnancies and in 10 pregnancies with severe fetal heart disease were reviewed. For each echocardiogram, three measurements of the cardiac axis were taken in the axial plane at the level of the four-chamber view. Differences in mean embryonic/fetal cardiac axis at different gestational ages in the healthy pregnancies were compared. RESULTS: The mean ± SD embryonic/fetal cardiac axis was 25.5 ± 11.5° from 8 + 0 to 9 + 6 weeks (Group 1), 40.4 ± 9.2° from 10 + 0 to 11 + 6 weeks (Group 2), 49.2 ± 7.4° from 12 + 0 to 12 + 6 weeks (Group 3), 50.6 ± 5.7° from 13 + 0 to 13 + 6 weeks (Group 4) and 48.6 ± 7.3° from 14 + 0 to 14 + 6 weeks (Group 5). Groups 1 and 2 were significantly different from each other and all other groups (P < 0.05). The results for 22 cases with repeat measurements from 8 + 0 to 11 + 6 and 12 + 0 to 14 + 6 weeks confirmed that the embryonic/fetal cardiac axis increased significantly (P < 0.001). In the cases with severe congenital heart disease, the cardiac axis was > 90th centile in four cases and < 10th centile in two cases. CONCLUSIONS: The embryonic cardiac axis is relatively midline at 8 weeks and levorotates in the late first trimester. By 12 weeks' gestation, the normal leftward fetal cardiac axis is established and remains stable until at least 14 + 6 weeks. Observation of an abnormal cardiac axis in some cases of severe congenital heart disease prior to 15 weeks' gestation may assist in prenatal detection.

Impact of a regional training program in fetal echocardiography for sonographers on the antenatal detection of major congenital heart disease.

OBJECTIVES: The aims of this study were to ascertain the effect of a regional training program in fetal echocardiography for obstetric radiographers on the antenatal detection of major congenital heart disease (CHD) and to document short-term outcomes for major CHD. METHODS: All 87 obstetric radiographers in Northern Ireland were invited to attend 2.5 days of training during a 1-year period. Data were collected before and after the training, over a 5-year study period, to assess the effect of training on the antenatal detection of CHD in the population. RESULTS: The antenatal detection of major CHD rose significantly, from 28% (72/262) pretraining to 43% (36/84) in the year of training (P = 0.008). Antenatal diagnosis of four-chamber-view defects rose significantly (from 38% to 54%; P = 0.04), as did detection of outflow-tract-view defects (from 8% to 21%; P = 0.05). Twelve per cent (13/108) of cases died spontaneously in utero and 8% (9/108) were terminated. Only 78% (67/86) of live-born cases in which CHD had been diagnosed antenatally survived the neonatal period, compared to 93% (221/238) with a postnatal diagnosis of CHD (P < 0.001). CONCLUSIONS: Even with a relatively simple training program, significant improvements can be made in the antenatal detection of CHD. With training, obstetric sonographers can successfully assess outflow tracts. Antenatally diagnosed cases have more complex CHD and this probably contributes to poor neonatal survival.