Population

We reviewed all cases of fetal CHD (including congenital cardiac defects and congenital cardiac abnormalities) referred to our institution between January 2002 and December 2011. The cohort consisted of fetuses born alive and delivered at our institution, and TOPs when the diagnosis was made at our center. We reviewed medical records of all fetuses from the time of fetal diagnosis to the last follow-up if born alive. For each case, we noted the presence of an ECM and whether it was diagnosed before birth or after birth.

The fetal karyotype and comparative genomic hybridization array, determined prenatally or postnatally, were recorded whenever available or were otherwise recorded as unknown. The anatomy of the cardiac defects was determined from postnatal echocardiography and surgical reports. The cardiac defects of all fetuses and inborn babies were classified in 10 groups, based on the anatomical and clinical ACC-CHD classification ; we added five more classes for non-structural cardiac abnormalities.

We classified the severity of the CHD according to the uni- or biventricular physiology of the defect for structural anomalies only. The physiology was determined according to the type of CHD for fetuses, and according to the effective surgery performed for children born alive. The postnatal outcome variable was mortality at last follow-up for children born alive.

Extracardiac anomalies

We included only major extracardiac anomalies, such as cytogenetic anomalies (aneuploidies and microdeletion syndromes) and major ECMs (e.g. diaphragmatic hernia, omphalocele, cerebral tumor, etc.) and polymalformative syndromes, which had at least two organ systems associated with the CHD. Minor ECMs were excluded for analysis; they were defined as an isolated ECM with limited clinical significance (e.g. hypospadias, hexadactylia).

Statistical analysis

The following groups were compared between TOP plus CC and live births (with active care): cytogenetic anomaly, overall ECM, ECM without cytogenetic anomaly (known before birth) and univentricular physiology. Bivariable categorical variables were expressed as frequencies and percentages, and associations were assessed using the χ ² test. We used a logistic binary regression model for multivariable adjustments. The associations are presented as odds ratios with 95% confidence intervals. A univariate analysis for time-event outcomes (death after excluding CC) was performed using the Kaplan–Meier model in the same groups: cytogenetic anomaly, overall ECM, ECM without cytogenetic anomaly and univentricular physiology. Survival between separate groups was compared using separate Kaplan–Meier analyses and tested for statistical significance using a log-rank test. A multivariable analysis was performed using the Cox proportional hazards model to determine independent prognostic factors of death, reported as hazard ratios and 95% confidence intervals. To avoid double counting, multivariable analyses excluded overall ECMs, and were assessed with the following three groups: cytogenetic anomaly, ECM without cytogenetic anomaly and univentricular physiology.

Statistical analyses were performed using SPSS software (SPSS, Inc., Chicago, IL, USA). A two-sided P -value < 0.05 was considered statistically significant.