Transcutaneous bilirubinometry in preterm infants

The aim of this study was to evaluate the accuracy and safety of transcutaneous bilirubinometry in preterm infants using the new bilirubin analyser BiliCheck^±. The study included 145 preterm children (23–36 wk gestation). Capillary blood sampling for determination of serum bilirubin (BS) was combined with transcutaneous bilirubin measurement (BTc) every morning until the sixth postnatal day and related to several clinical data (phototherapy (PT), infection signs, breathing disturbances, skin bleeding, etc.). Overall bilirubin concentration ranged from 17 to 371 μmol/l, and from 21 to 325 μmol/l for BS and BTc, respectively. Mean values obtained by BTc were significantly higher than BS values. The correlation coefficient between BS and BTc was r= 0.64 for the whole group, and r= 0.73 in infants without PT. As demonstrated by multiple regression analysis, BS‐BTc correlations were related only to gestational age (beta ‐0.32) and breathing disturbances (beta 0.29), indicating that the lower the gestational age and the more seriously ill the baby, the higher the incoherence between BS and BTc. Conclusion: BiliCheck^±provides a convenient, non‐invasive possibility for bilirubin estimation in preterm infants. However, there are limitations: the method gives reliable results only in newborns older than 30 wk gestation, without PT and artificial ventilation.     

Neonatal jaundice in 'healthy' very low birthweight infants

The daily bilirubin levels during the first week of life in 94 premature very low birthweight (VLBW, less than 1500 g) relatively 'healthy' infants were determined. Mean daily bilirubin values peaked on the fourth day of life at 188.1 mumol/l (s.e.m. = 5.3). Twenty-eight infants developed hyperbilirubinaemia (bilirubin greater than 260 mumol/l), at which time they were exposed to phototherapy. When individual peak bilirubin values were evaluated, the overall peak value was 213.9 mumol/l (s.e.m. = 5.1) occurring at 4.81 days (s.e.m. = 0.11), although the value is most likely an underestimate, since the 28 pre-phototherapy values were not truly peak values. Seventy-six (81%) infants experienced bilirubin levels greater than 170 mumol/l. The method of delivery apparently had no impact on the bilirubin levels. All the infants remained well and progressed satisfactorily. 'Healthy' VLBW infants experience a much greater incidence and severity of neonatal jaundice than mature infants with the same clinical status.     

Hyperbilirubinemia in preterm infants in Japan: New treatment criteria

In 1992, Kobe University proposed treatment criteria for hyperbilirubinemia in newborns using total serum bilirubin and serum unbound bilirubin reference values. In the last decade, chronic bilirubin encephalopathy has been found to develop in preterm infants in Japan because it can now be clinically diagnosed based on an abnormal signal of the globus pallidus on T2‐weighted magnetic resonance imaging and abnormal auditory brainstem response with or without apparent hearing loss, along with physical findings of kinetic disorders with athetosis. We therefore revised the Kobe University treatment criteria for preterm hyperbilirubinemic infants in 2017. The three revised points are as follows: (i) newborns are classified under gestational age at birth or corrected gestational age, not birthweight; (ii) three treatment options were created: standard phototherapy, intensive phototherapy, and albumin therapy and/or exchange blood transfusion; and (iii) initiation of standard phototherapy, intensive phototherapy, and albumin therapy and/or exchange blood transfusion is decided based on the total serum bilirubin and serum unbound bilirubin reference values for gestational weeks at birth at <7 days of age, and on the reference values for corrected gestational age at ≥7 days of age. Studies are needed to establish whether chronic bilirubin encephalopathy can be prevented using the 2017 revised Kobe University treatment criteria for preterm infants in Japan.     

Transcutaneous bilirubinometer in assessment of neonatal jaundice in northern India

This study was undertaken from April 2002 to March 2003 to find out the correlation of transcutaneous bilirubinometer index with serum bilirubin levels in term, pre-term, small for gestation age babies, with and without phototherapy in neonates with jaundice. Another aim was to evaluate the transcutaneous bilirubinometer as a screening device for neonatal hyperbilirubinemia by finding the action levels for TcBI at forehead and sternum at which sample for serum bilirubin estimation should be taken. A total of 104 neonates were evaluated. Mean (SD) age (hours), birth weight (grams) and gestational age (weeks) were 100.4 (37.90), 2264.9 (634.4) and 36.8 (2.9) respectively. Mean serum bilirubin was 16.6 (6) mg/dL. Overall a correlation coefficient of 0.878 at forehead and 0.859 at sternum was observed. On excluding infants receiving phototherapy coefficients of 0.900 at forehead and 0.908 at sternum were noted. Correlation coefficient over forehead and sternum was found to drop from 0.85 to as low as 0.33 with duration of phototherapy exceeding 48 hrs. Lastly the determined action levels had a sensitivity of 77.8 to 100 % in assessing the need for serum bilirubin estimation in various groups.     

Early corticosteroid treatment does not affect severity of unconjugated hyperbilirubinemia in extreme low birth weight preterm infants

Aim: To determine the relationship between early postnatal dexamethasone (DXM) treatment and the severity of hyperbilirubinemia in extreme low birth weight (ELBW) preterm infants. Methods: In 54 ELBW preterm infants, total serum bilirubin concentrations (TSB) and phototherapy (PT) data during the first 10 days were evaluated retrospectively. ELBW infants had participated in a randomized controlled trial of early DXM treatment which aimed to assess effects on chronic lung disease. Infants had been treated with DXM (0.25 mg/kg twice daily at postnatal day 1 and 2) or with placebo (normal saline). Analysis was performed on an intention to treat basis. Results: Twenty‐five Infants had been randomized into the DXM group; 29 into the placebo group. Mean (±SD) TSB [120 (±19) μmol/L vs. 123 (±28) μmol/L, DXM versus placebo, respectively] and maximum TSB [178 (±23) μmol/L vs. 176 (±48), DXM versus placebo, respectively] concentrations were similar. TSB concentrations peaked 30 h earlier in the DXM group (p ≤ 0.05). The need for PT as well as the duration of PT was similar in both groups. Conclusions: Early DXM treatment does not affect the severity of neonatal hyperbilirubinemia in ELBW preterm infants. Our results seem compatible with the concept that factors other than bilirubin conjugation capacity are important for the pathophysiology of neonatal jaundice in ELBW preterm infants.     

Value and limitations of bilirubin binding capacity in predicting the development of kernicterus

The serum bilirubin (SBR) and the bilirubin binding capacity (BBC) were determined on hospital admission in 181 consecutive neonates with neonatal jaundice. Twenty-three babies were less than 2500 g and two were of birth weight less than 2000 g. Fifteen babies were preterm. There were eight cases of kernicterus. Although the serum bilirubin was generally higher in infants with a BBC less than 34 mumol/l, there was no correlation between the bilirubin binding capacity and the presence of kernicterus (r = 0.28, P greater than 0.05). However, when both the serum bilirubin and the bilirubin binding capacity were used, a low value of BBC less than 34 mumol/l increased the risk of kernicterus. Higher values of BBC, on the other hand, did not mean that there was less risk of kernicterus, other factors being equal. This, while the bilirubin binding capacity may provide an additional source of information, its limitations should always be borne in mind.     

Predictors of significant jaundice in late preterm infants

Objectives

To study (i) the incidence and course of jaundice, and (ii) the predictors of ??significant jaundice?? in late preterm infants.

Design

Prospective analytical study.

Setting

Urban perinatal center.

Patients

Inborn late preterm infants (post menstrual age of 34 0/7 to 36 6/7 weeks).

Methods

Infants were followed till day 14 of life or till onset of significant jaundice. Relevant maternal, perinatal and neonatal variables were prospectively recorded. Transcutaneous bilirubin (TcB) was measured in each infant twice daily for the first 48 hours of life.

Outcomes

Significant jaundice defined as requirement of phototherapy/exchange transfusion as per hour specific total serum bilirubin (TSB) nomogram of AAP guidelines.

Results

216 infants were enrolled, of which 123 (57%) had significant jaundice. 36% of the jaundiced infants had TSB greater than 15 mg/dL. The mean duration of onset of significant jaundice was 61 ± 32 hours. The mean duration of phototherapy was 49 ± 26 hours. Large for gestation, lower gestational age, birth trauma and previous sibling with jaundice predicted severe jaundice. TcB measured at 24?C48 hrs was a better predictor of ??significant jaundice with onset after 48 hrs?? than clinical risk factors.

Conclusion

There is a high incidence of significant jaundice in late preterm infants. TcB measured at 24?C48 hrs of life better predicts ??significant jaundice after 48 hours of life??, in comparison with clinical risk factors.     

The Influence of Gestational Age and Birth Weight on the Infant Response to Phototherapy for Neonatal Hyperbilirubinaemia

A study evaluating the influence of gestational age and birth weight on the infant response to phototherapy for neonatal jaundice was attempted.
Phototherapy was equally effective in small for dates infants and premature infants of comparable size, and also in the small for dates infants and normal full size infants of comparable gestational age. Gestational age and infant size do not seem to play a significant role in determining infant response to phototherapy.     

BiliBlanket phototherapy system versus conventional phototherapy: A randomized controlled trial in preterm infants

Objective: This study compares the use of standard overhead fluorescent phototherapy units with the BiliBlanket a woven fibreoptic pad which delivers high intensity light with no ultraviolet or infrared irradiation in the treatment of jaundice in preterm infants.
Methodology: We chose to study infants between 800 and 2500 g, with strict criteria for commencing and ceasing phototherapy. Serum bilirubin levels were followed at 12–24 h intervals until 24 h after cessation of phototherapy. Infants were allocated at random to receive either conventional phototherapy or the BiliBlanket.
Results: There were 24 infants in the conventional group and 20 in the BiliBlanket group. Mean duration of phototherapy was compared and was 44 h for the conventional group versus 42 h for the BiliBlanket group.
Conclusions: We have shown that the BiliBlanket is as effective as conventional phototherapy and was well accepted by nursing staff and parents.     

Efficacy of phototherapy for hyperbilirubinaemia in infants with the respiratory distress syndrome

Objectives: To evaluate the efficacy of phototherapy for hyperbilirubinaemia in preterm infants with and without the respiratory distress syndrome (RDS).
Methodology: Prospective cohort study of preterm infants cared for at Kandang Kerbau Hospital, Singapore: 170 with RDS and 477 without RDS, sepsis or other complications (control group) presenting with non-haemolytic hyperbilirubinaemia at about the same time were exposed to daylight phototherapy when bilirubin concentrations exceeded 255 μmol/L or 222 μmol/L if <48h of age. Bilirubin values were monitored 6-hourly during exposure, and daily for at least 2 days postphototherapy.
Results The infants were comparable in birthweight, gestational age, postnatal age, haemoglobin, haematocrit and bilirubin values, at start. The response to phototherapy of the infants with RDS was comparable to that of the well preterm infants; the duration of exposure was 50.1 ± 1.6 (mean ± s.e.m.) versus 50.1 ± 1.4 h, 24-hour decline rate 25.71 ± 1.29% versus 26.32 ± 0.65, and overall decline rate 0.96± 0.03%/h versus 0.95±0.02%/h.
Conclusion The presence of RDS did not affect the efficacy of phototherapy for neonatal hyperbilirubinaemia in preterm infants.     

Prediction of the development of neonatal jaundice by increased umbilical cord blood bilirubin

Umbilical cord serum bilirubin concentration as a predictor of subsequent jaundice was studied in 291 newborns. It was possible to define subgroups of infants with significantly higher or lower risks of developing jaundice. If cord bilirubin was below 20 mumol/l, 2.9% became jaundiced as opposed to 85% if cord bilirubin was above 40 mumol/l. Furthermore, 57% of jaundiced infants with cord bilirubin above 40 mumol/l required phototherapy, but only 9% if cord bilirubin was 40 mumol/l or lower (p less than 0.003). Knowledge of infants at risk of developing jaundice allows simple bilirubin reducing methods to be implemented before jaundice is present and could influence a decision regarding early discharge from hospital. Since the ability of plasma to bind bilirubin in cord blood from jaundiced and non-jaundiced infants showed no significant differences, the increased cord bilirubin among infants who later became jaundiced is presumably caused by increased fetal bilirubin production or decreased removal of bilirubin from the fetal circulation.     

Neonatal jaundice in very low birth weight babies

Very low birth weight (VLBW) neonates born between January 1995 to December 1998, who survived for >2 days, were studied for the incidence, causes and interventions required for neonatal jaundice. Significant neonatal jaundice was defined as the total serum bilirubin (TSB) level beyond which baby required intervention (phototherapy and/or exchange transfusion) for neonatal jaundice. The incidence of significant neonatal jaundice (NNJ) was 76.6% and 37.3% required exchange transfusion. It was 82.9% at gestational age ≤28 weeks reduced whereas to 56.9% at gestational age of 35—36 weeks. The incidence was 75.3%, 78.5% and 76.7% in the birth weight group of 750—799 grams, 1000—1249 grams and 1250—1499 grams respectively. Glucose 6 phosphatase dehydrogenase (G-6-PD) deficiency (12.1%) was the commonest cause of jaundice. There is a need for evaluation of prophylactic therapies that enhances liver function or decreases production of bilirubin, which would prevent the rise of TSB to dangerous levels and thus would decrease the need for exchange transfusions.     

延迟脐带结扎对胎龄<32周早产儿的影响

目的评价延迟脐带结扎(DCC)对胎龄32周早产儿的影响。方法将2015年1~12月自然分娩的90例胎龄32周早产儿随机分为DCC组(46例)和早期结扎(ICC)组(44例),对比两组的血常规、红细胞输注总量、血气、平均动脉压、胆红素峰值、光疗总时间,以及坏死性小肠结肠炎、晚发性败血症、颅内出血和视网膜病、支气管肺发育不良的发生几率。结果 DCC组的血红蛋白、红细胞压积、平均动脉压、标准碱剩余(s BE)高于ICC组,而接受扩容及多巴胺升压治疗的早产儿比例以及红细胞输注量低于ICC组,差异有统计学意义(P0.05)。两组间体温、p H值、HCO3-浓度、血清胆红素峰值、总光疗时间以及晚发型败血症、视网膜病、Ⅱ级以上颅内出血及Ⅱ级以上新生儿坏死性小肠结肠炎的发生率差异无统计学意义(P0.05)。结论 DCC是一项安全的、可以改善胎龄32周早产儿预后的临床干预措施。     

Utility of a new transcutaneous jaundice device with two optical paths in premature infants

BACKGROUND: Hyperbilirubinemia may cause dysfunction of the central nervous system of newborn infants. Recently, a new transcutaneous bilirubin device has been developed, which is not limited by maturity or melanin concentration of the skin. However, there have been few reports limiting the subjects to preterm and very low-birthweight (VLBW) infants. METHODS: Transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) were measured within 1 h of time lag in 50 premature infants. TcB was measured with the new jaundice device on the forehead. TSB samples were measured by direct colorimetry. The correlation coefficient and regression line were calculated. RESULTS: The results showed a good correlation between TcB and TSB. However, the correlation tended to be worse with infants whose birthweights were lower than 1000 g, or whose gestational ages at birth were shorter than 28 weeks. CONCLUSION: TcB and TSB have a close correlation, and TcB tends to be higher than TSB. The Minolta transcutaneous jaundice device could be used as a screening instrument, leading to the avoidance of invasive blood samplings for preterm and VLBW infants. However, in patients whose birthweights are lower than 1000 g or whose gestational ages are shorter than 28 weeks, care must be taken when using the transcutaneous jaundice device because of low reliability in these patients.     

Improvement in auditory and visual evoked potentials in jaundiced preterm infants after exchange transfusion.

Two preterm infants with peak serum bilirubin concentrations of 270 mumol/l and 200 mumol/l, respectively showed improvement in the wave peak latencies of the auditory and visual evoked potentials after exchange transfusion. The implications of this observation and the use of evoked potential recording in neonatal jaundice are discussed.     

脐血胆红素预测新生儿黄疸的意义

目的研究脐带血胆红素水平预测足月健康新生儿后续黄疸程度的价值。方法523例足月健康新生儿,测定脐血胆红素、白蛋白水平,监测每日经皮胆红素值（TCB）。对时龄0—24hTCB≥18;-48hTCB≥21;-72hTCB≥25;〉72h≥25者,送检静脉血血清胆红素值（TSB）,考虑是否需要光疗。将新生儿按脐血胆红素水平分为〈30μmol／L;≥30μmoL／L;≥36μmol／L;≥42μmoL／L,共4组。比较4组新生儿TCB≥25、TSB〉205μmol／L、TSB〉257μmoL／L及需要光疗的发生率。对脐血胆红素水平预告新生儿黄疸进行分析。比较黄疸组新生儿和非黄疸组新生儿临床特征。结果脐血胆红素水平升高,各组新生儿TCB≥25、TSB〉205μmol／L、TSB〉257μmoL／L和需要光疗的发生率增加。脐血胆红素水平用于预测新生儿黄疸发生有统计学意义（P〈0．001）。黄疸组新生儿脐血胆红素值显著高于非黄疸组（t=10．96,P〈0．001）。而脐血清白蛋白值（t=2．38,P〉0．05）、妊娠周数（t=-0．90,P〉0．05）、出生体重（t=0．10,P〉0．05）比较,两组均无统计学差异。结论脐血胆红素水平用于预测足月健康新生儿后续黄疸的程度是一种有效的方法。     

Screening for neonatal hyperbilirubinaemia and ABO alloimmunization at the time of testing for phenylketonuria and congenital hypothyreosis

In a population-based study including 2463 infants, serum bilirubin measurements were added to the neonatal screening programme for phenylketonuria and congenital hypothyreosis. This screening programme detected 11/17 (65%) of infants with serum bilirubin levels > 350/μmol l⁻¹, of whom 7 (3 per 1000) were readmitted from home (6 treated with phototherapy). A total of 139 infants (5.6%) received phototherapy. Maternal blood type O occurred significantly more often in term infants treated (30/54; 55.6%) compared with preterm infants treated (32/85; 37.6%) and with blood type O occurrence in the total population of mothers (906/2426; 37.3%) ( p < 0:05). The blood type constellations mother O/infant A or B showed a sensitivity of 64%, specificity 65%, positive predictive value 12% and a negative predictive value of 96% for the requirement of phototherapy for the whole material. Exchange transfusion was not required in any of the infants. No infant developed bilirubin encephalopathy (kernicterus). Adding bilirubin to a neonatal screening programme detects some cases with unexpectedly high bilirubin levels in need of intervention. Routine ABO blood typing of pregnant women, ABO cord blood typing and Coombs' test in infants of mothers with blood type O cannot be recommended because of low positive predictive value for the requirement of intervention (phototherapy) by these tests.     

Developmental changes in serum half-life of (EZ)-cyclobilirubin

BACKGROUND: Phototherapy has been a standard treatment for neonatal hyperbilirubinemia for more than 40 years, but it has remained sub-optimal. AIMS: To clarify the developmental changes in parameters of (4E, 15Z)-cyclobilirubin ((EZ)-C) elimination in order to obtain basic data for establishing optimal phototherapy. STUDY DESIGN: Blood samples were taken at regular intervals after stopping phototherapy, and bilirubin fractions were analyzed by high-performance liquid chromatography. SUBJECTS AND METHODS: The subjects were 46 infants with hyperbilirubinemia who underwent phototherapy. The gestational age and birth weight of the subjects ranged from 25.0 to 41.0 weeks and from 656 to 3810 g, respectively, and the age at cessation of phototherapy was a median of 5 days. A kinetic model of (EZ)-C elimination was established, and the serum half-life of (EZ)-C was calculated on the basis of the determined model. Relationships of the half-life of (EZ)-C with birth weight and gestational age were investigated. RESULTS: Serum (EZ)-C elimination followed a first-order kinetic model in 43 infants and a zero-order kinetic model in three extremely low birth weight infants. The half-life of (EZ)-C calculated on the basis of a first-order elimination model in serum ranged from 68 to 274 min and showed weak negative correlations with birth weight and gestational age. CONCLUSIONS: Serum (EZ)-C excretion followed a first-order kinetic model in most of the neonates. The half-life of (EZ)-C becomes more prolonged in the very low birth weight infant and early gestational age.     

Breast milk jaundice in premature infants.

In randomised study of 186 preterm infants those fed on maternal or banked breast milk had a significantly higher peak bilirubin concentration and a more prolonged jaundice than infants fed an artificial preterm formula and were over four times more likely to achieve plasma bilirubin values above 200 mumol/l (11.7 mg/100 ml). This dietary effect was seen even in a high risk subgroup of sick ventilated infants below 1500 g who were receiving restricted enteral intakes. We suggest that breast milk jaundice in preterm infants may increase clinical intervention. Our findings are discussed in the light of epidemiological data suggesting an association between moderate hyperbilirubinaemia (greater than 170 mumol/l) and neurodevelopmental outcome.     

Randomized trial of prophylactic phototherapy in the infant with very low birth weight

Twenty-two preterm infants (birth weight 850 +/- 220 gm) were randomly assigned to receive phototherapy either soon after birth or after the serum bilirubin concentration reached 5 mg/dl. Infants receiving prophylactic phototherapy were placed under lights at a significantly earlier age and lower serum bilirubin concentration than infants in the routine group (P less than 0.001). There was no significant difference between groups in peak serum bilirubin concentration, age at which it peaked, rate of rise in serum bilirubin concentration, or serum bilirubin concentration at any time during the study. Infants assigned to the prophylactic phototherapy group were under lights for a significantly longer time than those in the routine group (P less than 0.05). There was a significant rise in both configurational and structural photo-isomers (P less than 0.005) independent of serum bilirubin concentration after phototherapy in all patients. These data suggest that the clinical course of hyperbilirubinemia is not altered in infants with very low birth weight receiving prophylactic phototherapy compared with infants with phototherapy begun at a bilirubin concentration of 5 mg/dl.