Jaundiced Babies Research Articles

Brain stem electric response audiometry in neonates with hyperbilirubinemia.

Auditory evoked responses using BERA were studied in 30 newborn babies with plasma bilirubin > or = 15 mgm/dl and repeated after treatment of neonatal jaundice with bilirubin levels of < or = 10 mgm/dl. A few jaundiced babies (16.5%) showed absent BERA response at the initial/subsequent examination. After treatment, 3/30 babies showed absent wave form responses and 2 of these were clinically kernicteric. Jaundiced babies had prolonged wave peak latencies and inter peak latencies. Treated babies showed a tendency towards recovery in their BERA responses which were however not complete. Total plasma bilirubin value at the time of BERA examination and mean maximal bilirubin values had no correlation with the incidence and degree of BERA abnormalities.

Glucose‐6‐phosphate dehydrogenase deficiency, neonatal tetanus and neonatal jaundice in Nigeria: Clinical observation

In a study of 92 cases of neonatal tetanus (NNT), it was found that 23 (25%) had associated neonatal jaundice (NNJ) but in none of them was NNJ severe enough to cause kernicterus. Glucose‐6‐Phosphate dehydrogenase (G‐6‐PD) deficiency was less common in babies with NNT than expected in general population (p 0.02). These babies with NNT were as exposed to icterogenic agents as jaundiced babies previously reported from the same institution. The lower incidence of G‐6‐PD deficiency in babies with NNT was probably due to the fact that G‐6‐PD deficient babies on exposure to icterogenic agents develop severe NNJ early and may die of kernicterus. Antibiotic therapy in jaundiced babies may prevent NNT in some of the G‐6‐PD deficient babies who are more prone to severe NNJ. More of the G‐6‐PD normal babies therefore remained at home till they develop NNT. It is speculated that steps taken to prevent NNJ in the G‐6‐PD deficient babies by avoiding application of potentially infected icterogenic agents (i.e. menthol c...

Increased incidence of hyperbilirubinaemia in ‘unchallenged’ glucose-6-phosphate dehydrogenase deficiency in term Saudi newborns

The incidence of severe hyperbilirubinaemia was significantly higher among the G6PD-deficient Saudi infants born at term than in non-deficient babies (34% vs 9%) (p less than 0.005). No apparent offending factors were detected in either the babies or their mothers. All babies who developed hyperbilirubinaemia did so during the 1st week of life. The highest mean bilirubin level for all jaundiced G6PD-deficient babies was recorded on the 4th postnatal day. Although the incidence of severe hyperbilirubinaemia among our neonates was relatively high, only two of them (7%), a boy and a girl, required exchange transfusions. Five of 29 jaundiced babies with G6PD deficiency were readmitted after discharge because of significant jaundice. One required exchange transfusion. Since G6PD deficiency seems to be a relatively common cause of neonatal jaundice in Saudi newborns, early detection of this enzymopathy by cord blood screening is justified to avoid morbidity and deaths.

Inadequate Breast Feeding and Jaundice

To the Editor.— It is not surprising that Kemper et al1 found that mothers of jaundiced babies were more likely to wean their infants before le month of age than those mothers whose infants were not jaundiced. However, one aspect of this problem was not discussed in their article. Is it not possible that not only might mothers stop breast-feeding earlier because of the jaundice, but also that the jaundice itself might be a symptom of inadequate feeding and therefore result in earlier termination of breast-feeding?

Unconjugated bilirubin and the bile from light exposed Gunn rats inhibit intestinal water and electrolyte absorption.

Jaundiced babies undergoing phototherapy often develop diarrhoea. The cause of it is still uncertain. Increasing evidence supports a role of a secretory mechanism for the diarrhoea. We therefore studied the effects of bile from congenitally jaundiced rats undergoing phototherapy and of unconjugated bilirubin on rat small intestine in vivo and in vitro. Results suggest that: (1) the bile from homozygous Gunn rats under phototherapy has an anti-absorptive effect when tested in the perfused jejunum of normal Wistar rats; (2) unconjugated bilirubin has a dose dependent secretory effect on the intestinal transport of water and electrolytes, when tested in the same system. Alteration of cyclic AMP or cyclic GMP, known intracellular mediators of secretion, was not observed. We conclude that free bilirubin is an intestinal secretagogue acting by an as yet unknown mechanism, that may mediate the secretory type of diarrhoea in jaundiced neonates undergoing phototherapy.

Light effects on transport and excretion of bilirubin in newborns.

There is now firm evidence that phototherapy has the following effects on bilirubin metabolism in humans with unconjugated hyperbilirubinemia. It rather rapidly converts a substantial fraction of the normal toxic 4Z, 15Z form of bilirubin to the 4Z, 15E form, which probably is less toxic. Simultaneously it enhances the overall excretion of bilirubin by converting it to oxidation products and structural and configurational isomers that are excretable in bile and urine without the need for glucuronidation. We know that these reactions occur in vivo because we have synthesized the compounds involved and have identified them unambiguously in vivo in the tissues of jaundiced babies and rats undergoing phototherapy. It is unlikely that these photobiological effects on bilirubin metabolism and transport are restricted to babies undergoing purposeful phototherapy. All babies are exposed to visible light and all develop hyperbilirubinemia during early life, with many exhibiting jaundice. Because there is no lower intensity threshold for photochemical reactions, it seems probable that the photobiological effects described in this paper occur in most newborns to some degree. Furthermore, similar photoprocesses would be expected to occur in the approximately 2-5% of the population who have the benign condition known as Gilbert's syndrome, which is characterized by chronic mild unconjugated hyperbilirubinemia, particularly when they sunbathe. Clearly, in the particular instance of phototherapy of neonatal jaundice, blue light is therapeutic. In some respects it acts like a drug, almost like the ideal magic bullet, because it is specific for the target molecule and safe. The main limitation of phototherapy is that it is inefficient, a limitation that seems to be imposed by transport processes in the body and the optics of skin rather than by the photochemical reactions on which it depends.

DETECTION OF DONOR'S LYMPHOCYTES IN THE PERIPHERAL BLOOD OF NEONATES FOLLOWING EXCHANGE-TRANSFUSION

Twenty preterm and term female neonates were exchange-transfused with males donor fresh blood during their first days of life because of hyperbilirubinaemia or severe septicaemia. In order to study the presence of donor lymphocytes in the neonates peripheral blood, chromosome studies were performed immediately after,12 and 72 hours following the exchange transfusion. We used the fluorescent-binding technique in order to distinguish the donor's cells by the presence of the γ-chromosone or other fluorescent markers in at least 300 mitotic figures in each speciment. We found that in jaundiced babies immediately following exchange transfusion less than 10% of the lymphocytes came from the donor and 12 hours later only 1-2% were still present.However in neonates exchange-transfusion for septicaemia the percentage of donor's lymphocytes immediately following the proceedure sometimes reached 50% and dropped to less than 10% by 12 hours.This shows the inability of the depressed by the infection host defence mechanisms of the newborn to deal with the donor's lymphocytes.

Birth weight, and use of oxytocin and analgesic agents in labour in relation to neonatal jaundice.

A prospective study of 1977 babies, delivered in two district hospitals in the Northern Tablelands area of New South Wales, revealed a highly significant relationship between neonatal jaundice and birth weight in all cases of neonatal jaundice (P = 0.0001). The use of oxytocin was associated with a significant increase in the incidence of jaundice (all cases, P = 0.003; severely jaundiced babies, P = 0.05). This effect was related to the total dose of oxytocin used (P = 0.003 for all cases; P = 0.056 for severely jaundiced babies), but not to its rate of administration. No significant difference was apparent whether oxytocin was administered to initiate or to accelerate labour. The suggestion that oxytocin use is associated with delivery of immature babies is refuted. The use of analgesic agents during labour was not associated with an increased incidence of neonatal jaundice.

In vivo Hemoperfusion Studies of Bilirubin Removal from Jaundiced Dogs

Removal of bilirubin by hemoperfusion (HP) on a macroreticular ion-exchange resin is suggested as a novel clinical procedure for the treatment of jaundiced newborn babies. The efficiency and biocompatibility of the proposed macroreticular (MR) ion exchange column was tested in vivo with jaundiced dogs. An animal model with a choledocho-suprarenal vein shunting allowed to test the column capacity for the adsorption of conjugated and unconjugated bilirubin. A second animal model, based on infusing unconjugated bilirubin directly into the blood stream, enabled to test the column operation at desired unconjugated bilirubin concentrations. The results of the in vivo hemoperfusion tests are very encouraging and compare favorably with bilirubin removal from babies by exchange transfusion (ET). Operating a column containing 10 ml resin per kg body weight for 3 hours removed over 1.7 times the initial unconjugated bilirubin content. Furthermore, the animals seemed to be unaffected by the HP procedure; the changes due to hemoperfusion on blood chemistry, hematology and some hormone levels were practically insignificant.

Is Kernicterus Always the Definitive Evidence of Bilirubin Toxicity?

Concluding an extensive clinical and pathologic study of 126 cases of kernicterus, Gerrard wrote in 1952: "The pigmentation of the brain is secondary to the nerve cells being first damaged by a factor or factors unknown."1 This opinion was shared by most of the experts of this period. Systematic measurements of bilirubin levels in jaundiced newborns were not part of their management. In the absence of such measurements the jaundiced babies with kernicterus did not appear to be different from the larger number of jaundiced newborns without kernicterus.

Phototherapy-induced covalent binding of bilirubin to serum albumin.

Bilirubin displays a detectable fluorescence emission only when it is complexed with serum albumin, whereas free bilirubin has a very low fluorescence yield. Actually, nearly complete disappearance of bilirubin emission was obtained when the unirradiated human serum albumin-bilirubin complex was precipitated with acetone to extract the pigment; complete removal of protein-bound bilirubin (as monitored by fluorescence spectroscopy) was achieved by repeating the acetone extraction after incubation of the complex in the phosphate buffer, pH 7.4, containing 7 M guanidinium chloride; the latter compound causes on extensive unfolding of protein molecules. On the other hand, in the case of irradiated solutions, even after denaturation of the protein with 7 M guanidinium chloride, a detectable amount of bilirubin-type fluorescent material was found to be associated with albumin. This finding clearly shows that bilirubin and/or some photoproduct underwent in part a photoinduced covalent binding with human serum albumin. Fragmentation of the bovine albumin polypeptide chain according to the procedure detailed in the experimental section yielded only one peptide-containing material fluorescent in the 530 nm region. This fact underlines the selective nature of the photobinding reaction. The amino acid composition of the isolated peptide is shown in Table 2; the composition is closely similar with that found for peptide 187-397 of native bovine serum albumin. In the case of the jaundiced babies who were subjected to phototherapy, we were able to demonstrate that only after 7 to 9 hr of exposure to light a detectable amount of bilirubin-type fluorescent material was present even at the end of the serum treatment with acetone and guanidinium chloride (see Fig. 1; Table 1). Fractional precipitation of the serum proteins by addition of controlled amounts of ammonium sulphate showed that the fluorescent material was present only in the albumin fraction. The photoadduct disappeared about 15 to 20 days after the phototherapy had been discontinued. This period of time represents the natural turnover period of human serum albumin.

The Effect of Phototherapy on Neonatal Vitamin D Metabolism

Phototherapy for the treatment of neonatal jaundice has now been widely accepted. Its effect on Vitamin D metabolism is however unknown. In this study 10 full-term jaundiced babies receiving phototherapy were investigated. Serum 25OHD, 24,25(OH)2D, Ca and P were measured. Samples were taken before the onset of phototherapy, 48 hours after the onset and 24 hours after the finish of phototherapy. The mean weight of the 10 babies was 3.4 kg, mean age of onset of phototherapy 64 hours of age,mean bilirubin level at onset 17.1mg%. The mean duration of phototherapy was 83 hours. Causes of jaundice were G6PD deficiency (1), rhesus incompatibility (1), blood group incompatibility (3), and unknown (5). Infants were nursed naked under the phototherapy light which was provided by seven daylight fluorescent lamps 60 cm above the baby. Babies were fed a cow's milk formula not containing Vit. D. The mean serum 25OHD and serum 24,25(OH)2D before phototherapy were 8.49±6.91 ng/ml and 1.29±2.64 respectively, 48 hours after the onset were 8.72±6.10 and 0.84±1.53 and 24 hours after the finish were 7.51±5.34 and 0.46±0.74 respectively. Mean calcium values before and 24 hours after the finish of phototherapy were 9.36±1.10 mg% and 9.83±0.93 mg%. Likewise mean phosphate values were 6.19±1.58 and 7.35±0.97 mg%. The results of this preliminary study thus suggest that the neonatal jaundiced skin does not convert provitamin D to active Vitamin D in response to phototherapy light (420λ). Neither was hypo or hypercalcaemia observed after phototherapy as has been previously reported.

Blue light and bilirubin excretion.

Blue light converts bilirubin in the skin of jaundiced rats to metastable geometric isomers that are transported in blood and excreted in bile. The same reaction probably occurs in jaundiced babies exposed to light, particularly during treatment with phototherapy. Excretion of unisomerized bilirubin is prevented by intramolecular hydrogen bonding, and the pigment has to be metabolized to more polar derivatives to be excreted efficiently.

Clinical study of prolonged jaundice in breast- and bottle-fed babies.

A study of 893 births was undertaken to determine the incidence of prolonged neonatal jaundice. 55% of these babies were breast feeding on discharge from the maternity hospital. Jaundice lasting for 3 weeks or more was found in 12 breast-fed term babies (2-4% of all breast-fed babies), and in no bottle-fed infant. 3 of the jaundiced babies gained weight poorly in the first 3 weeks of life, but after that age failure to thrive was not associated with the prolonged jaundice. The hyperbilirubinaemia, which persisted in 11 infants from between 21 to 80 days (mean 39 days), was due to elevations in both conjugated and unconjugated fractions.

Biliary Obstruction in the Newborn

Looking at the problem of biliary atresia from the vantage point of 30 years’ experience with the lesion, we can say with certainty that the jaundiced baby who has had no extrahepatic bile duct has been the most disappointing patient for the surgeon in the whole realm of lesions theoretically correctable by a surgical procedure.

The Response of Leukocytes in the Peripheral Blood During and Following Exchange Transfusion in the Newborn

Serial leukocyte counts were done on 12 full-term and eight premature jaundiced babies during exchange transfusions and daily thereafter until the ninth day, in order to study changes in each cell type. The main changes were found to be (1) a marked reduction in all cell types during the procedure with a statistically significant difference in absolute values before and after; (2) significantly lower values of the polymorphonuclear neutrophils and eosinophils in the baby's blood at the end of the transfusion compared with those of the donor's blood, with the monocytes and lymphocytes showing no statistically significant change; and (3) a remarkable rise in each cell type starting soon after the procedure and reaching a peak within the week following the transfusions. Comparison of absolute values during the post-transfusion days with those found in normal babies of corresponding postnatal age showed that the polymorphonuclear neutrophils and eosinophils were significantly increased, the lymphocytes unchanged, and the absolute values of monocytes decreased compared to those of normal babies.

Jaundice associated with bacterial infection in the newborn.

The occurrence of jaundice in babies seriously ill with bacterial infection is well recognized. This series of 22 newborn infants demonstrates that bacterial infection and jaundice may be associated, without severe constitutional upset and with few abnormal clinical signs or laboratory findings. There were no deaths in this series. Urinary tract infection was present in nine babies. Bacterial infection should be considered as the possible cause of neonatal jaundice, whatever the clinical condition of the baby.

Clinical Paediatric Surgery: Diagnosis and Management.

This book of modest size deals with the extensive field of pediatric surgery in condensed form suited to the needs of medical students, general practitioners, and pediatricians. The book covers common subjects in all fields of pediatric surgery, including orthopedic and neurosurgical areas. It offers the advantage of discussing in more detail the symptoms, methods of diagnosis, and overall treatment of the child with a wide variety of surgical problems. Many conditions are discussed under specific symptoms to guide the resident in evaluating his patient. Thus, for common clinical problems such as vomiting in the first month of life, the jaundiced newborn baby, and surgical causes of failure to thrive, this volume offers a systematic discussion and meaningful differential diagnosis. An attempt to cover the broad field of pediatric surgery and its specialties within a reasonable volume required the exclusion of much information on a number of serious, but rare

Sequelae of neonatal jaundice.

A total of 371 newborn infants falling into 3 groups, non-haemolytic jaundice, haemolytic jaundice, and non-jaundiced controls, have been reassessed in the 6th year of life as regards neurological, audiological, and psychological function. Neurological handicap was concentrated among the infants of low birth weight and was not related to jaundice, apart from one case of athetoid cerebral palsy with deafness. No other cases of perceptive deafness were discovered. Intelligence testing on the Stanford Binet scale showed no relation between depth of jaundice and I.Q. These findings support the majority of reports in the literature that reduction in intelligence does not occur in non-haemolytic jaundiced babies with serum bilirubin below about 20 mg./100 ml. In haemolytic jaundice slight doubt remains. There is no indication for changing present standards for exchange transfusion.

Sequelae of neonatal jaundice.

A total of 371 newborn infants falling into 3 groups, non-haemolytic jaundice, haemolytic jaundice, and non-jaundiced controls, have been reassessed in the 6th year of life as regards neurological, audiological, and psychological function. Neurological handicap was concentrated among the infants of low birth weight and was not related to jaundice, apart from one case of athetoid cerebral palsy with deafness. No other cases of perceptive deafness were discovered. Intelligence testing on the Stanford Binet scale showed no relation between depth of jaundice and I.Q.These findings support the majority of reports in the literature that reduction in intelligence does not occur in non-haemolytic jaundiced babies with serum bilirubin below about 20 mg./100 ml. In haemolytic jaundice slight doubt remains. There is no indication for changing present standards for exchange transfusion.