Abstract: Twenty-one studies met our inclusion criteria (N = 457,202 participants). Nineteen studies provided data for the primary analysis (oxygen saturation threshold < 95% or ≤ 95%; N = 436,758 participants). The overall sensitivity of pulse oximetry for detection of CCHD was 76.3% (95% confidence interval [CI] 69.5 to 82.0) (low certainty of the evidence). Specificity was 99.9% (95% CI 99.7 to 99.9), with a false-positive rate of 0.14% (95% CI 0.07 to 0.22) (high certainty of the evidence). Summary positive and negative likelihood ratios were 535.6 (95% CI 280.3 to 1023.4) and 0.24 (95% CI 0.18 to 0.31), respectively. These results showed that out of 10,000 apparently healthy late preterm or full-term newborn infants, six will have CCHD (median prevalence in our review). Screening by pulse oximetry will detect five of these infants as having CCHD and will miss one case. In addition, screening by pulse oximetry will falsely identify another 14 infants out of the 10,000 as having suspected CCHD when they do not have it. The false-positive rate for detection of CCHD was lower when newborn pulse oximetry was performed longer than 24 hours after birth than when it was performed within 24 hours (0.06%, 95% CI 0.03 to 0.13, vs 0.42%, 95% CI 0.20 to 0.89; P = 0.027). Forest and ROC plots showed greater variability in estimated sensitivity than specificity across studies. We explored heterogeneity by conducting subgroup analyses and meta-regression of inclusion or exclusion of antenatally detected congenital heart defects, timing of testing, and risk of bias for the "flow and timing" domain of QUADAS-2, and we did not find an explanation for the heterogeneity in sensitivity. Pulse oximetry is a highly specific and moderately sensitive test for detection of CCHD with very low false-positive rates. Current evidence supports the introduction of routine screening for CCHD in asymptomatic newborns before discharge from the well-baby nursery.

Plain-language summary: We searched until March 2017 for evidence on use of pulse oximetry to detect CCHD in newborn infants and found 21 studies. These studies used different thresholds to define a pulse oximetry test as positive. We combined all studies using a threshold around 95% (19 studies with 436,758 newborn infants). This review found that for every 10,000 apparently healthy newborn infants screened, around six of them will have CCHD. The pulse oximetry test will correctly identify five of these newborn infants with CCHD (but will miss one case). Newborn infants who are missed could die or experience major morbidity. For every 10,000 apparently healthy newborn infants screened, 9994 will not have CCHD. The pulse oximetry test will correctly identify 9980 of them (but 14 newborn infants will be investigated for suspected CCHD). Some of these infants may be exposed to unnecessary additional tests and a prolonged hospital stay, but a proportion will have a potentially serious non-cardiac illness. The number of newborn infants incorrectly investigated for CCHD decreases when pulse oximetry is performed longer than 24 hours after birth. We judged the included studies to be mainly at low or unclear risk of bias for several of the certainty domains assessed. Some studies used less robust methods to verify negative results. We considered the overall certainty of the evidence as moderate.