Background
Focus of guidelines
Methods of statement development
Level | Definition |
---|---|
1a | Systematic review (with homogeneity) of RCTs |
1b | Individual RCT (with narrow confidence interval) |
2a | Systematic review (with homogeneity) of cohort studies |
2b | Individual cohort study |
3a | Systematic review (with homogeneity) of case–control studies |
3b | Individual case–control study |
4 | Case-series (and poor quality cohort and case–control studies) |
5 | Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles” |
Acute bilirubin encephalopathy
-
Birth asphyxia
-
Severe hypothermia (Tc < 36°C for > 6 hours)
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Respiratory failure (RDS, pneumonia, meconium aspiration syndrome)
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Prolonged acidosis (pH < 7.20 for > 6 hours)
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Severe hypoglycaemia (glucose < 45 mg/dl for > 12 hours)
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Severe haemolysis
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Sepsis and meningitis
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Drugs impairing bilirubin/albumin binding
Bilirubin measurement
Prediction of hyperbilirubinaemia
h | 50th | 75th | h | 50th | 75th | h | 50th | 75th |
---|---|---|---|---|---|---|---|---|
24
|
6, 3
|
7, 8
| 49 | 7, 7 | 10, 4 | 73 | 10 | 11, 7 |
25 | 6, 3 | 7, 8 | 50 | 7, 8 | 10, 4 | 74 | 10 | 11, 8 |
26 | 6, 4 | 7, 8 | 51 | 8 | 10, 5 | 75 | 10, 1 | 11, 9 |
27 | 6, 4 | 7, 9 | 52 | 8, 1 | 10, 5 | 76 | 10, 1 | 11, 9 |
28 | 6, 4 | 7, 9 | 53 | 8, 3 | 10, 6 | 77 | 10, 2 | 12 |
29 | 6, 5 | 7, 9 |
54
|
8, 4
|
10, 6
|
78
|
10, 2
|
12, 1
|
30
|
6, 5
|
7, 9
| 55 | 8, 6 | 10, 7 | 79 | 10, 3 | 12, 2 |
31 | 6, 6 | 8, 1 | 56 | 8, 7 | 10, 8 | 80 | 10, 4 | 12, 2 |
32 | 6, 6 | 8, 4 | 57 | 8, 9 | 11 | 81 | 10, 5 | 12, 3 |
33 | 6, 7 | 8, 6 | 58 | 9 | 11, 1 | 82 | 10, 5 | 12, 3 |
34 | 6, 7 | 8, 8 | 59 | 9, 2 | 11, 2 | 83 | 10, 6 | 12, 4 |
35 | 6, 8 | 9, 1 |
60
|
9, 3
|
11, 3
|
84
|
10, 7
|
12, 4
|
36
|
6, 8
|
9, 3
| 61 | 9, 4 | 11, 3 | 85 | 10, 7 | 12, 4 |
37 | 6, 9 | 9, 4 | 62 | 9, 5 | 11, 4 | 86 | 10, 8 | 12, 4 |
38 | 7, 1 | 9, 5 | 63 | 9, 6 | 11, 4 | 87 | 10, 8 | 12, 4 |
39 | 7, 2 | 9, 7 | 64 | 9, 6 | 11, 4 | 88 | 10, 8 | 12, 4 |
40 | 7, 3 | 9, 8 | 65 | 9, 7 | 11, 5 | 89 | 10, 9 | 12, 4 |
41 | 7, 5 | 9, 9 |
66
|
9, 8
|
11, 5
|
90
|
10, 9
|
12, 4
|
42
|
7, 5
|
10
| 67 | 9, 8 | 11, 5 | 91 | 10, 9 | 12, 5 |
43 | 7, 5 | 10, 1 | 68 | 9, 8 | 11, 5 | 92 | 10, 9 | 12, 5 |
44 | 7, 6 | 10, 1 | 69 | 9, 9 | 11, 6 | 93 | 10, 9 | 12, 6 |
45 | 7, 6 | 10, 2 | 70 | 9, 9 | 11, 6 | 94 | 10, 9 | 12, 6 |
46 | 7, 6 | 10, 2 | 71 | 9, 9 | 11, 6 | 95 | 10, 9 | 12, 7 |
47 | 7, 6 | 10, 3 |
72
|
9, 9
|
11, 6
|
96
|
10, 9
|
12, 7
|
48
|
7, 6
|
10, 3
|
h | 50th | 75th | 90th | h | 50th | 75th | 90th | h | 50th | 75th | 90th |
---|---|---|---|---|---|---|---|---|---|---|---|
24
|
6.1
|
7.5
|
8.9
| 49 | 9.0 | 10.3 | 11.9 | 73 | 10.0 | 11.7 | 13.2 |
25 | 6.2 | 7.7 | 9.1 | 50 | 9.1 | 10.4 | 12.0 | 74 | 10.0 | 11.8 | 13.3 |
26 | 6.4 | 7.8 | 9.2 | 51 | 9.1 | 10.4 | 12.1 | 75 | 10.1 | 11.8 | 13.3 |
27 | 6.5 | 8.0 | 9.3 | 52 | 9.2 | 10.5 | 12.2 | 76 | 10.1 | 11.8 | 13.4 |
28 | 6.7 | 8.2 | 9.5 | 53 | 9.2 | 10.6 | 12.3 | 77 | 10.2 | 11.9 | 13.4 |
29 | 6.8 | 8.3 | 9.6 |
54
|
9.3
|
10.7
|
12.4
|
78
|
10.2
|
11.9
|
13.5
|
30
|
7.0
|
8.5
|
9.7
| 55 | 9.3 | 10.8 | 12.5 | 79 | 10.3 | 12.0 | 13.5 |
31 | 7.2 | 8.6 | 9.9 | 56 | 9.3 | 10.8 | 12.5 | 80 | 10.3 | 12.1 | 13.6 |
32 | 7.3 | 8.7 | 10.1 | 57 | 9.3 | 10.9 | 12.6 | 81 | 10.4 | 12.1 | 13.7 |
33 | 7.5 | 8.9 | 10.2 | 58 | 9.4 | 10.9 | 12.7 | 82 | 10.5 | 12.2 | 13.7 |
34 | 7.7 | 9.0 | 10.5 | 59 | 9.4 | 11.0 | 12.8 | 83 | 10.6 | 12.3 | 13.8 |
35 | 7.9 | 9.1 | 10.6 |
60
|
9.5
|
11.0
|
12.9
|
84
|
10.6
|
12.4
|
13.8
|
36
|
8.0
|
9.2
|
10.8
| 61 | 9.5 | 11.1 | 12.9 | 85 | 10.6 | 12.4 | 13.9 |
37 | 8.1 | 9.3 | 10.8 | 62 | 9.5 | 11.1 | 12.9 | 86 | 10.7 | 12.5 | 14.0 |
38 | 8.2 | 9.4 | 10.9 | 63 | 9.5 | 11.2 | 12.9 | 87 | 10.7 | 12.5 | 14.1 |
39 | 8.3 | 9.5 | 10.9 | 64 | 9.6 | 11.2 | 13.0 | 88 | 10.7 | 12.5 | 14.2 |
40 | 8.4 | 9.6 | 11.0 | 65 | 9.6 | 11.3 | 13.0 | 89 | 10.8 | 12.6 | 14.3 |
41 | 8.5 | 9.7 | 11.1 |
66
|
9.6
|
11.3
|
13.0
|
90
|
10.8
|
12.6
|
14.4
|
42
|
8.6
|
9.8
|
11.1
| 67 | 9.6 | 11.4 | 13.0 | 91 | 10.9 | 12.7 | 14.5 |
43 | 8.7 | 9.9 | 11.2 | 68 | 9.6 | 11.4 | 13.1 | 92 | 11.0 | 12.9 | 14.6 |
44 | 8.7 | 9.9 | 11.3 | 69 | 9.7 | 11.5 | 13.1 | 93 | 11.2 | 13.0 | 14.7 |
45 | 8.8 | 10.0 | 11.5 | 70 | 9.8 | 11.6 | 13.1 | 94 | 11.3 | 13.2 | 14.8 |
46 | 8.9 | 10.1 | 11.6 | 71 | 9.8 | 11.7 | 13.2 | 95 | 11.4 | 13.4 | 14.9 |
47 | 8.9 | 10.2 | 11.7 |
72
|
9.9
|
11.7
|
13.2
|
96
|
11.5
|
13.5
|
15.0
|
48
|
9.0
|
10.2
|
11.8
|
Hours of life | TP | FN | TN | FP | Sensitivity | Specificity | PPV | NPV |
---|---|---|---|---|---|---|---|---|
24 - 48 hours
| ||||||||
<50th percent | 27 | 0 | 161 | 460 | 100% | 25.9% | 5.5% | 100% |
<75th percent | 25 | 2 | 429 | 192 | 92.6% | 69.1% | 11.5% | 99.5% |
<90th percent | 14 | 13 | 564 | 57 | 51.9% | 90.8% | 19.7% | 97.7% |
49 - 72 hours
| ||||||||
<50th percent | 21 | 0 | 410 | 615 | 100% | 40% | 3.3% | 100% |
<75th percent | 21 | 0 | 702 | 323 | 100% | 68.5% | 6.1% | 100% |
<90th percent | 18 | 3 | 888 | 137 | 85.7% | 86.6 | 11.6% | 99.7% |
73 - 96 hours
| ||||||||
<50th percent | 7 | 0 | 246 | 220 | 100% | 52.8% | 3.1% | 100% |
<75th percent | 7 | 0 | 348 | 118 | 100% | 74.7% | 5.6% | 100% |
<90th percent | 5 | 2 | 409 | 57 | 71.4% | 87.8% | 8.1% | 99.5% |
Hours of life | TP | FN | TN | FP | Sensitivity | Specificity | PPV | NPV |
---|---|---|---|---|---|---|---|---|
24 - 48 hours
| ||||||||
<50th percent | 24 | 1 | 357 | 263 | 96.0% | 57.6% | 8.4% | 99.7% |
<75th percent | 22 | 3 | 479 | 141 | 88.0% | 77.3% | 13.5% | 99.4% |
<90th percent | 12 | 13 | 576 | 44 | 48.0% | 92.9% | 21.4% | 97.8% |
49 - 72 hours
| ||||||||
<50th percent | 23 | 0 | 657 | 368 | 100% | 64.1% | 5.9% | 100% |
<75th percent | 22 | 1 | 860 | 165 | 95.7% | 83.9% | 11.8% | 99.9% |
<90th percent | 17 | 6 | 975 | 50 | 73.9% | 95.1% | 25.4% | 99.4% |
73 - 96 hours
| ||||||||
<50th percent | 7 | 0 | 322 | 145 | 100% | 69.0% | 4.6% | 100% |
<75th percent | 7 | 0 | 409 | 58 | 100% | 87.6% | 10.8% | 100% |
<90th percent | 6 | 1 | 446 | 21 | 85.7% | 95.5% | 22.2% | 99.8% |
-
All jaundiced newborn infants should be tested with a TcB measurement and the value should be plotted on the hour-specific nomogram for TcB measurements (Table 2).
-
If the TcB measurement is > 75th percentile, a serum determination of bilirubin should be performed and the value should be plotted on the nomogram for TSB measurements (Table 3).
-
Newborn infants with a TSB value < 50th percentile in the first 48 hours of live and babies with a value < 75th percentile after 48 hours of life are not at risk of hyperbilirubinaemia and do not require further evaluations.
-
Newborn infants with a TSB value > 50th percentile in the first 48 hours of live and babies with a value > 75th percentile after 48 hours of life are at risk of hyperbilirubinaemia and should be tested again after 24 or 48 hours according to the hours of life and the presence of clinical risk factors.
Treatment: phototherapy
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Phototherapy should be administered for irradiating the most of the infant’s skin.
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Intensive phototherapy with an irradiance > 35 μW/cm2/nm is recommended. Daylight, blue light, conventional or blue LED phototherapy can be used (evidence level 1a).
-
Fiberoptic phototherapy can be used even if it is less effective than conventional phototherapy and require more prolonged treatment (evidence level 1a) [37].
-
Serum bilirubin should be tested 4–8 hours after the beginning of phototherapy or earlier if TSB < 3 mg/dL less than threshold for exchange transfusion. Subsequently, TSB should be assessed every 12–24 hours to monitor the treatment effectiveness.
-
In case of treatment failure, multiple phototherapy should be started adding a fiberoptic device to the conventional treatment to increase the skin’s exposure (evidence level 1a) [37].
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Phototherapy should be discontinued once the bilirubin levels are below the threshold value for treatment on two consecutive measurements, 6–12 h apart. This would avoid keeping babies under phototherapy longer than necessary [38] (evidence level 1b).
-
Serum bilirubin should be checked 12–24 hours after discontinuation of phototherapy the occurrence of post-phototherapy bilirubin rebound [39] (evidence level 4).
-
Infants with either Rhesus or ABO haemolytic disease should be immediately treated with phototherapy once the diagnosis is made.
Exchange transfusion (ET)
-
ET should be performed only by trained personnel in a neonatal intensive care unit with fully monitoring and resuscitation capabilities.
-
Heart rate, breath rate, SpO2 and body temperature should be monitored during ET and for 12–24 hours after the end of the procedure.
-
The most common adverse effects of ET are thrombocytopenia, haemolysis, hypocalcaemia, hypotension, venous thrombosis, hypokalaemia and hypoglycaemia and should be carefully monitored.
-
Measurement of TSB should be performed before ET and at the end of the procedure.
-
As bilirubin levels may continue to rise after an ET we recommend that TSB is measured every 4–6 hours, and that phototherapy is continued.
-
It is recommended to discontinue enteral feeding during ET and for 6 hours from the end of the procedure (evidence level 5).
-
Infants underwent ET should be followed up for the development of anaemia after discharge.