ABC | Volume 111, Nº5, November 2018

Original Article Lopes et al Mortality for critical congenital heart diseases and newborns Arq Bras Cardiol. 2018; 111(5):666-673 The literature indicates that premature newborn infants with a low Apgar score, and who require invasive ventilatory support, are those who present higher risk of mortality when more complex procedures are required. 12,13 The objective of this article was to describe the mortality, fatality, and survival rates of CHD newborns in a Brazilian large urban center, as well as to characterize the associated risk and morbidity factors. Methods A nested case-control study cohort was performed, paired with newborns selected by lot, born in the city of Salvador (state of Bahia) and in its respective metropolitan region, from December 2014 to January 2016. The original sample was a case-control study paired by maternal age and newborn age, in which 52 cases of critical and complex CHD were selected in the neonatal period. Data were prospectively collected in the four largest public maternity hospitals in the city of Salvador. All newborns were placed in the process of regulation to a specialized center, but they did not undergo any interventional procedure until transfer, since none of the maternities had a cardiac surgery service. The follow-up and the recording of newborns monitoring were performed up to the moment of discharge from the maternity ward (due to clinical improvement, transference or death). The independent variables were: gestational age, low birth weight (weight less than < 2,500 grams), pulse oximetry test (POT), cardiac auscultation (presence or absence of murmur or irregular heart rhythm), Apgar, twinning, and presence of comorbidities (neonatal sepsis, and respiratory insufficiency, with demand for invasive ventilatory support). The dependent variable was the occurrence of critical and/ or complex CHD, and the secondary outcome was death. The CHD cases included were the critical CHD newborns, which were channel-type or shunt-dependent, or considered complex (those with three or more defects), born in the services included in the study, in the reported period. For the comparison group, the neonates without CHD were included, selected by lot, of the same gender of the case, with more than 24 hours of life who, on physical examination, did not present murmurs or arrhythmias, with pre- and post-ductal oximetry, and differential not exceeding 3% and above 95% saturation. Considering a possible fallibility of POT, and aiming at minimizing possible losses, these newborns were followed by telephone or at the childcare outpatient clinic up to 3 months after discharge from the maternity ward. In addition, in order to minimize possible losses, and to identify allocation errors, in the first year after completion of data collection, all newborns and infants entries were monitored in the only public high-complexity pediatric cardiac surgery service of the state of Bahia. Newborns whose only identified heart disease was the presence of Patent Arterial Duct (PAD), or other simple heart diseases; with pulmonary hypertension without structural heart disease; cases that were not characterized as CHD; newborns whose parents or guardians did not sign the Free and Informed Consent Form (FICF) were excluded from the study. This study was approved by the Research Ethics Committee (CEP) of Hospital Ana Nery and by the local Ethics Committees of each hospital involved (CAAE: 17970413200000045). The FICF was used to make the child’s legal guardian aware of the process. For the proportional mortality calculations, mortality data were used in the neonatal period, for the same sampled population and period studied. Sample size estimation was performed primarily for the case-control study, considering the proportion of exposed cases within of 20%; proportion of exposed, among controls/ comparison group of 11.11%,%; Odds Ratio (OR) 2; and significance level of 5% (test power: 80%). Statistical analysis For the direct estimation of gross relative risks, we chose to perform simple Poisson regression modeling, associated to the robust estimation of standard errors, aiming to control some possible average violation of the assumption of equality between mean and variance of the distribution of Poisson, and consequent more adequate estimation of the model p values, and level of significance of 5%. 14 For the calculation of the Confidence Intervals of 95% (95% CI), the use of the Delta 2 method was added. The model goodness of fit was evaluated by analyzing the residual deviance and the Akaike Information Criterion (AIC). 15 In the Kaplan-Meier survival curves analysis, Cox regression modeling with right censorship was used to obtain survival probability and hazard ratio (HR), assuming proportionality risk. For the comparison of the survival curves, Log rank test was used. The database was created in Epidata, 16 version 3.1, and the statistical analyzes were performed in the statistical package R, version 3.2.3. 17 Results Fifty-two cases of CHD newborns with critical and complex congenital heart disease and their respective comparison groups, in the maternity hospitals studied, were identified and monitored. The most frequent heart diseases were formation of aortic arch defects, which depended on the ductus arteriosus (62 cases/100,000 live births), followed by pulmonary atresia with or without hypoplasia of the right ventricle (53 cases/100,000 births), and transposition of the great arteries (38 cases/100,000 live births). As a consequence of gender pairing, the distribution was equal between the groups (OR: 0.92; 95% CI: 0.67-1.27]). In the initial data, there was one case of ambiguous genitalia; however, during follow-up it was confirmed that it was a female newborn. The risk of death among newborn infants with CHD was twice as high among premature infants (RR: 2.14; 95% CI [1.22-3.75]; p = 0.003), with low birth weight (RR: 2.14; 95% CI [1.22-3.75]; p < 0.0001) and Apgar < 7 in the first minute of life (RR: 2.08; 95% CI [1.13-3.82]; p = 0.017). The presence of some comorbidity, besides CHD, was associated with the outcome, and increased the risk by almost three times (p < 0.0001). There was a higher proportion of 667