Background and Objectives: Neonatal hypoglycemia, a common metabolic problem, often goes unnoticed owing to lack of specific symptoms. The Canadian Paediatric Society gives permission to print single copies of this document from our website. AbstractHyperbilirubinemia is very common and usually benign in the term newborn infant and the late preterm infant at 35 to 36 completed weeks’ gestation. Kernicterus – the pathological finding of deep-yellow staining of neurons and neuronal necrosis of the basal ganglia and brainstem nuclei.
Acute bilirubin encephalopathy – a clinical syndrome, in the presence of severe hyperbilirubinemia, of lethargy, hypotonia and poor suck, which may progress to hypertonia (with opisthotonos and retrocollis) with a high-pitched cry and fever, and eventually to seizures and coma. Chronic bilirubin encephalopathy – the clinical sequelae of acute encephalopathy with athetoid cerebral palsy with or without seizures, developmental delay, hearing deficit, oculomotor disturbances, dental dysplasia and mental deficiency [1]-[3].
The prevention, detection and management of jaundice in otherwise healthy term and late preterm newborn infants remain a challenge, partly because jaundice is so common and kernicterus is so rare in comparison [4]-[6]. Milder degrees of hyperbilirubinemia not leading to a clinical presentation of acute encephalopathy may also be neurotoxic and cause less severe long-term complications. Acute bilirubin encephalopathy was first recognized in infants with rhesus hemolytic disease; this etiology is now largely avoidable and, consequently, has become rare. Several risk factors have been identified for the development of severe hyperbilirubinemia in the newborn (Table 1). A search was carried out in MEDLINE and the Cochrane library and was last updated in January 2007. Carefully timed TSB measurements can be used to predict the chances of developing severe hyperbilirubinemia.
Therefore, the best available method for predicting severe hyperbilirubinemia appears to be the use of a timed TSB measurement analyzed in the context of the infant’s gestational age. Although bilirubin is derived from the breakdown of hemoglobin, routine umbilical cord blood hemoglobin or hematocrit measurement does not aid in the prediction of severe hyperbilirubinemia [30] (evidence level 2b).
The usual antenatal screen for a panel of red cell antibodies occasionally identifies additional mothers who will deliver infants at increased risk of hemolysis. Newborns with glucose-6-phosphate dehydrogenase (G6PD) deficiency have an increased incidence of severe hyperbilirubinemia (evidence level 1b).
Exhaled carbon monoxide is increased during hemolysis; however, prediction of severe hyperbilirubinemia is not improved by measuring the end-tidal carbon monoxide concentration [44] in addition to a timed TSB measurement (evidence level 1b). All mothers should be tested for ABO and Rh(D) blood types and be screened for red cell antibodies during pregnancy (recommendation grade D [Table 3]). If the mother was not tested, cord blood from the infant should be sent for evaluation of the blood group and a DAT (Coombs test) (recommendation grade D). Blood group evaluation and a DAT should be performed in infants with early jaundice of mothers of blood group O (recommendation grade B). Selected at-risk infants (Mediterranean, Middle Eastern, African or Southeast Asian origin) should be screened for G6PD deficiency (recommendation grade D).
A test for G6PD deficiency should be considered in all infants with severe hyperbilirubinemia (recommendation grade D). Previous recommendations were to measure TSB concentration in all infants with clinical jaundice at any time in the first four days of life, and to measure TSB concentration in those who are not clinically jaundiced but have increased risk factors. The peak TSB concentration usually occurs between three and five days of life, at which time the majority of babies have already been discharged from hospital. If the TSB concentration had not been measured earlier because of clinical jaundice, a TSB measurement should be obtained at the same time as the metabolic screening test to avoid an increase in the number of painful procedures and to minimize costs; alternatively, a TcB measurement should be obtained either at discharge or before 72 h of life.
Some of the most severely affected infants require therapy to be started before the time of the metabolic screen to prevent severe hyperbilirubinemia and its complications.
In addition to universal measurement, all newborns should be clinically assessed for jaundice repeatedly within the first 24 h, and again, at a minimum, 24 h to 48 h later.
It is possible to measure bilirubin concentration using capillary or venous blood samples or transcutaneously. Displacement of bilirubin from albumin-binding sites by certain toxic medications and additives has caused numerous cases of kernicterus in the past, mostly in the neonatal intensive care unit population [54]. Although early neonatal jaundice is generally due to unconjugated hyperbilirubinemia, in some situations the conjugated fraction may be elevated, such as in rhesus erythroblastosis, liver disease and cholestasis [59]. Either TSB or TcB concentration should be measured in all infants during the first 72 h of life.
If the TSB concentration does not require immediate intervention, the results should be plotted on the predictive nomogram. Any infant discharged before 24 h of life should be reviewed within 24 h by an individual with experience in the care of the newborn who has access to testing and treatment facilities (recommendation grade D). There should be a systematic approach to the risk assessment of all infants before discharge and institution of follow-up care if the infant develops jaundice (recommendation grade D). All newborns who are visibly jaundiced in the first 24 h of life should have their bilirubin level determined (recommendation grade D). Transcutaneous bilirubinometry is an acceptable method, either as a routine procedure or in infants with visible jaundice.
TSB concentration may be estimated on either a capillary or a venous blood sample (recommendation grade C). Infants with severe or prolonged hyperbilirubinemia should be further investigated, including measurement of the conjugated component of bilirubin (recommendation grade C). Although breastfed infants are at a higher risk for developing severe hyperbilirubinemia than are formula-fed infants, the known risks of acute bilirubin encephalopathy are very small when weighed against the substantial known benefits of breastfeeding [17][63].
Phenobarbitone, studied as a means of preventing severe hyperbilirubinemia in infants with G6PD deficiency [69], did not improve clinically important outcomes (evidence level 1b). Synthetic analogues of heme oxygenase, such as tin-mesoporphyrin (SnMP), strongly inhibit its activity and suppress the production of bilirubin. A quasi-RCT (73; n=142) was unable to find clinical benefit of prophylactic phototherapy in ABO isoimmunization (evidence level 2b). Phototherapy can be used both to prevent severe hyperbilirubinemia in infants with a moderately elevated TSB concentration and as initial therapy in those with severe hyperbilirubinemia. The energy from light induces a conformational change in the bilirubin molecule, making it water soluble; light in the blue-green part of the spectrum is most effective. Phototherapy decreases the progression to severe hyperbilirubinemia in infants with moderate hyperbilirubinemia (evidence level 1a) [12]. In general, fluorescent light is most commonly used [81]; the intensity of light produced by fluorescent tubes wanes over time. Intensive phototherapy for infants with severe hyperbilirubinemia or those at greatly elevated risk of developing severe hyperbilirubinemia.
A useful online tool is available for deciding whether intensive phototherapy would be recommended by these guidelines [82].
Intravenous immunoglobulin (IVIG) reduces bilirubin concentrations in newborns with rhesus hemolytic disease and other immune hemolytic jaundice. SnMP, studied for preventing the progression of moderate hyperbilirubinemia [88], showed no evidence of reduction in clinically important outcomes (evidence level 1a). There is observational evidence that offering supplemental oral fluids may interfere with the eventual duration of breastfeeding [78] (evidence level 2b), but such studies were not performed in the context of brief supplementation in the setting of neonatal jaundice, and a systematic review of intervention studies found no reliable evidence [91].
Oral agar to prevent enterohepatic reuptake of bilirubin is not supported by the available evidence [92]-[95] (evidence level 1b).
A program for breastfeeding support should be instituted in every facility where babies are delivered (recommendation grade D). Routine supplementation of breastfed infants with water or dextrose water is not recommended (recommendation grade B). A TSB concentration consistent with increased risk (Figure 1) and (Table 4) should lead to enhanced surveillance for development of severe hyperbilirubinemia, with follow-up within 24 h to 48 h, either in hospital or in the community, and repeat estimation of TSB or TcB concentration in most circumstances (recommendation grade C). Intensive phototherapy should be given according to the guidelines shown in Figure 2 (recommendation grade D). Supplemental fluids should be administered, orally or by intravenous infusion, in infants receiving phototherapy who are at an elevated risk of progressing to exchange transfusion (recommendation grade A).
An infant who presents with severe hyperbilirubinemia, or who progresses to severe hyperbilirubinemia despite initial treatment, should receive immediate intensive phototherapy. If phototherapy fails to control the rising bilirubin concentrations, exchange transfusion is indicated to lower TSB concentrations. Infants with a TSB concentration above the thresholds shown on Figure 3 should have immediate intensive phototherapy, and should be referred for further investigation and preparation for exchange transfusion (recommendation grade B).
An infant with clinical signs of acute bilirubin encephalopathy should have an immediate exchange transfusion (recommendation grade D).
Routine newborn surveillance, whether in hospital or after discharge, should include assessment of breastfeeding and jaundice every 24 h to 48 h until feeding is established (usually on the third or fourth day of life). The occurrence of severe hyperbilirubinemia mandates an investigation of the cause of hyperbilirubinemia. Adequate follow-up should be ensured for all infants who are jaundiced (recommendation grade D). Infants requiring intensive phototherapy should be investigated for determination of the cause of jaundice (recommendation grade C). Severe hyperbilirubinemia in relatively healthy term or late preterm newborns (greater than 35 weeks’ gestation) continues to carry the potential for complications from acute bilirubin encephalopathy and chronic sequelae. AcknowledgementsThis position statement was reviewed by the Canadian Paediatric Society’s Community Paediatrics Committee and the College of Family Physicians of Canada. Ip S, Chung M, Kulig J, et al; American Academy of Pediatrics, Subcommittee on Hyperbilirubinemia. Continue phototherapy until the serum bilirubin level is lower than the threshold range or until the infant is well and there is no jaundice of palms and soles. If the bilirubin level is very high (see table) and you can safely do exchange transfusion, consider doing so. Normal glucose range – buzzle, It is very important, that each one knows what is the normal glucose range. Blood glucose levels: testing and normal range, A blood glucose test measures the amount of a type of sugar, called glucose, in your blood.
AbstractBackgroundControversies surround a diagnosis of gestational diabetes mellitus (GDM).
We designed this study to assess the incidence of hypoglycemia in healthy normal birth weight and low birth weight babies, including both preterm and small for gestational age (SGA) newborns, to evaluate the impact of early breastfeeding on hypoglycemia and to assess the impact of exclusive breast feeding on glucose values up to 48 h of age. Study of blood glucose level in normal and low birth weight newborns and impact of early breast feeding in a tertiary care centre.
The overall prevalence depends on birth weight, gestational age and intrauterine growth retardation. Insulin and glucagon during the perinatal period: secretion and metabolic effects on the liver. Controversies regarding definition of neonatal hypoglycemia- suggested operational threshold. Blood glucose levels in a population of healthy breast-fed term infants of appropriate size for gestational age.
Incidence of hypoglycemia in newborn infants classified by birth weight and gestational age.
Critical hyperbilirubinemia is uncommon but has the potential for causing long-term neurological impairment. This remains controversial; however, if there are bilirubin concentrations at which subtle cerebral injury can occur, the thresholds are unknown [13]-[15].
The Canadian Paediatric Surveillance Program (CPSP) recently reported 258 full-term infants over a two-year period (2002 to 2004) who either required exchange transfusion or had critical hyperbilirubinemia (excluding infants with rhesus isoimmunization) [18]. Reports [22][23] indicate that acute bilirubin encephalopathy continues to occur in otherwise healthy infants with, and occasionally without, identifiable risk factors.
Search terms in MEDLINE were hyperbilirubinemia and newborn, and the clinical queries filter of Haynes et al [25] was applied using the broad, sensitive option. Infants of less than 38 weeks’ gestation whose TSB concentration is greater than the 75th percentile have a greater than 10% risk of developing severe hyperbilirubinemia; similarly, infants of 39 to 40 weeks’ gestation whose TSB concentration is above the 95th percentile have a greater than 10% risk (evidence level 2b). Babies whose mothers are blood group O have an OR of 2.9 for severe hyperbilirubinemia (because most infants with jaundice due to ABO isoimmunization are blood group A or B infants born to a mother with group O blood)[31][32]. The significance of the various antibodies differs; in such infants, analysis of blood group and a DAT is usually required, closer follow-up and earlier therapy may be needed, and a consultation with a paediatric hematologist or neonatologist is suggested.
Testing for G6PD deficiency in babies whose ethnic group or family history suggest an increased risk of G6PD deficiency is advised (eg, Mediterranean , Middle Eastern, African [37] or Southeast Asian origin).


Because of the high occurrence of the risk factors, this recommendation requires TSB measurement in a large majority of infants (exceptions include females of certain ethnic groups who are fully formula fed and more than 37 weeks’ gestation). At the usual age of discharge, TSB concentrations that are in a high-risk zone on the nomograms cannot be reliably detected by visual inspection, especially in infants with darker skin colours. The prediction of severe hyperbilirubinemia is more accurate if the gestational age at birth is included in the prediction model [28].
Sudden increases in TSB concentration may also occasionally occur after the first two to three days [47]. This should be performed by an individual competent in the assessment of the newborn who can, if necessary, immediately obtain a TSB or TcB measurement and arrange treatment for the infant, whether in hospital or after discharge.
There is no systematic difference between the results of capillary or venous samples [48][49]. It is believed to be free bilirubin (ie, not bound to albumin) that crosses the blood-brain barrier and causes neuronal damage [55]-[57].
In infants placed on phototherapy, measurement of the conjugated fraction should be considered.
If not required earlier because of clinical jaundice, a TSB measurement should be obtained at the same time as the metabolic screening test; alternatively, a TcB measurement should be obtained either at discharge or, if not yet discharged, at 72 h of life (recommendation grade C). The result of the TSB measurement, the time at which it was obtained and the zone should be recorded, and a copy should be given to the parents.
The result should be summed with the 95% CI of the device to estimate the maximum probable TSB concentration (recommendation grade C). Support of the breastfeeding mother by knowledgeable individuals increases the frequency and duration of breastfeeding. In a study [70] with historical controls in infants with G6PD deficiency, SnMP eliminated the need for phototherapy and appeared to prevent severe hyperbilirubinemia. The effectiveness of phototherapy is related to the area of skin exposed and the intensity of the light at the skin at the relevant wavelengths [74]-[76]. Some infants with jaundice are dehydrated, and rehydration will usually lead to a prompt fall in the TSB concentration; enteral feeding should be continued because it will replace missing fluid, supply energy and reduce enterohepatic reuptake of the bilirubin [80]. A program of biomedical support for ensuring adequate light intensity is important to assure effective therapy.
In usual clinical situations, this will require two phototherapy units, or special high-intensity fluorescent tubes, placed approximately 10 cm from the infant, who can be nursed in a bassinet. It acts as a completive inhibitor for those antibodies that cause red cell destruction, release hemoglobin and cause jaundice [47].
The frequency of exchange transfusion was significantly reduced by the extra fluids from 54% to 16% [89] (evidence level 1b). The frequency of exchange transfusion in the infants in the study noted above was very high [92]; the same absolute risk reduction from extra fluids will not be seen in a population with a much lower likelihood of requiring exchange. The bilirubin concentration should be checked within 2 h to 6 h of initiation of treatment to confirm response.
All jaundiced infants, especially high-risk infants and those who are exclusively breastfed, should continue to be closely monitored until feeding and weight gain are established and the TSB concentration starts to fall. Investigations should include a clinically pertinent history of the baby and the mother, family history, description of the labour and delivery, and the infant’s clinical course [35].
Careful assessment of the risk factors involved, a systematic approach to the detection and follow-up of jaundice with the appropriate laboratory investigations, along with judicious phototherapy and exchange transfusion when indicated, are all essential to avoid these complications.
Developmental follow-up of breastfed term and near-term infants with marked hyperbilirubinemia. Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Kernicterus: Epidemiological strategies for its prevention through systems-based approaches. Are moderate degrees of hyperbilirubinemia in healthy term neonates really safe for the brain?
Predicting the risk of jaundice in full-term healthy newborns: A prospective population-based study. Optimal search strategies for retrieving scientifically strong studies of treatment from Medline: Analytical survey.
Combining clinical risk factors with serum bilirubin levels to predict hyperbilirubinemia in newborns.
An early (sixth-hour) serum bilirubin measurement is useful in predicting the development of significant hyperbilirubinemia and severe ABO hemolytic disease in a selective high-risk population of newborns with ABO incompatibility.
Prevalence and lack of clinical significance of blood group incompatibility in mothers with blood type A or B.
Readmission for newborn jaundice: The value of the Coombs’ test in predicting the need for phototherapy. Studies in hemolysis in glucose-6-phosphate dehydrogenase-deficient African American neonates. Neonatal hyperbilirubinaemia in heterozygous glucose-6-phosphate dehydrogenase deficient females.
Noninvasive measurement of total serum bilirubin in a multiracial predischarge newborn population to assess the risk of severe hyperbilirubinemia. Recognition of the presence and severity of newborn jaundice by parents, nurses, physicians, and icterometer. The effect of instituting a prehospital-discharge newborn bilirubin screening program in an 18-hospital health system. The objective of this study was to evaluate the oral glucose tolerance test (OGTT) for the prediction of adverse gestational and perinatal outcomes in pregnant women with a positive screening test for diabetes mellitus and a negative diagnosis, i.e. Since quite a proportion of neonates do not manifest any symptoms despite existence of hypoglycemia, exact incidence is difficult to work out. A clinical report from American Academy of Pediatrics, Committee on Fetus and Newborn Pediatrics. ABM Clinical Protocol#1: Guidelines for glucose monitoring and treatment of hypoglycemia in breastfed neonates. Early discharge of the healthy newborn infant, particularly those in whom breastfeeding may not be fully established, may be associated with delayed diagnosis of significant hyperbilirubinemia. The collaborative perinatal project, examining 54,795 live births in the United States, was unable to find any consistent association between peak TSB concentrations below critical levels and IQ or other adverse outcomes [12].
Twenty per cent of these infants had at least one abnormal neurological sign at presentation, and 5% had documented hearing loss or significant neurological sequelae at discharge. Prevention of this rare but serious disease requires appropriate clinical assessment, interpretation of TSB concentration and treatment, which must include all systems involved in the provision of health care and community support. They are of limited use in directing surveillance, investigation or therapy by themselves, but can be useful in combination with timed TSB analysis.
Other searches without the filter were carried out to find publications addressing specific issues. When the TSB concentration was below the 40th percentile at the time of measurement, there were no cases of subsequent TSB concentration greater than the 95th percentile. The need for phototherapy is increased in ABO-incompatible infants who are direct antiglobulin test (DAT [direct Coombs test])-positive compared with those who are DAT-negative [28][30].
Although G6PD deficiency is an X-linked disease, female heterozygotes can have more than 50% of their red cells deficient in the enzyme because of random inactivation of the X chromosome. Despite these recommendations, infants continue to present with severe hyperbilirubinemia during or after their initial hospitalization. To predict the occurrence of severe hyperbilirubinemia, it is therefore recommended that either TSB or TcB concentration be measured in all infants between 24 h and 72 h of life; if the infant does not require immediate treatment, the results should be plotted on the predictive nomogram to determine the risk of progression to severe hyperbilirubinemia. Capillary sampling is the method used most often in Canada and in most studies, including those of Bhutani et al [9]. The clinical value of measurement of free bilirubin is currently uncertain and it is not readily available [58]. However, previous reports [16][20] on the epidemiology of bilirubin toxicity use the TSB concentration as the standard, which remains the deciding value for phototherapy and other therapies. Follow-up of the infant should be individualized according to the risk assessment (recommendation grade D). It is difficult to find reliable evidence that the risk of severe jaundice can be minimized by a program of breastfeeding support, but other aspects of breastfeeding difficulty can be reduced by such programs, and providing such support is reasonable (evidence level 5) [60]. However, prospective RCTs have as yet failed to demonstrate a clinically important benefit (evidence level 1b), and the compounds are not commercially available [71][72]. More intense phototherapy can be achieved using multiple phototherapy units [77] or simply moving the unit closer to the infant. Fibre optic phototherapy systems were introduced in the late 1980s; the advantages are that the baby can be breastfed without interruption of phototherapy and eye pads are not required, but the disadvantage is that the peak intensity is less than that of fluorescent systems. The duration of phototherapy did not differ between the groups, and no other clinically important outcomes were affected.
Oral fluids appear to be as effective as intravenous fluids [90] during intensive phototherapy (evidence level 1b). Therefore, in breastfed infants, extra fluids are indicated for, but should be restricted to, infants with an elevated risk of requiring exchange transfusion (evidence level 1b). Consideration of further therapy should commence and preparations for exchange transfusion may be indicated. Because blood collected after an exchange transfusion is of no value for investigating many of the rarer causes of severe hyperbilirubinemia, these investigations should be considered before performing the exchange transfusion.
In other words, symptomatic hypoglycemia is not common (1-3 per 1000 live births) as against chemical hypoglycemia [67% in preterm small for gestational age (SGA) to 4% in term appropriate for gestational age (AGA)].
Guidelines for the prediction, prevention, identification, monitoring and treatment of severe hyperbilirubinemia are presented. Therefore, prevention of acute encephalopathy remains the justification for the prevention, detection and treatment of severe hyperbilirubinemia [16][17]. During this period, the live birth rate in Canada was approximately 330,000 per year, leading to a calculated minimal incidence of this degree of severity of hyperbilirubinemia of approximately four in 10,000 live births.
It should also be noted that although a large number of studies have demonstrated an increased risk of severe hyperbilirubinemia with breastfeeding, one study [24] found that exclusive breastfeeding was associated with a lower incidence of hyperbilirubinemia.
The hierarchy of evidence from the Centre for Evidence-Based Medicine was applied using levels of evidence for both treatment and prognosis [26] (Table 2). When the TSB concentration was between the 40th and the 75th percentiles, only 2.2% of infants developed a TSB concentration greater than the 95th percentile.
Universal testing for incompatibility with blood grouping, and for isoimmunization using the DAT, on cord blood does not improve clinical outcomes compared with testing only infants whose mothers are group O [33][34] (evidence level 2b). Females with greater proportions of their red cells affected have an increased risk of severe neonatal hyperbilirubinemia [38]; therefore, testing of both girls and boys who are at risk is advised [39].
Recent data from the CPSP [18] demonstrated that 185 of 289 infants with critical hyperbilirubinemia presented after hospital discharge. The TSB (or TcB) concentration and the predictive zone should be recorded, a copy should be given to the family at the time of discharge, and follow-up arrangements should be made for infants who are at higher risk (Table 4).
Therefore, the institution of a program of universal screening complements, but does not replace, careful ongoing assessment of newborn infants beginning from the first hours of life and continuing through the first weeks. There are several limitations to TcB measurements [50]: they become unreliable after initiation of phototherapy [51], and they may be unreliable with changes in skin colour and thickness [52]. Exclusively breastfed infants experience their maximum weight loss by day 3 and lose, on average, 6% to 8% of their birth weight [64]. Although phototherapy increases water loss from transepidermal skin, this is not a clinically important issue in full-term infants who are drinking well.
Halogen spotlights may also be used, but they must not be placed closer to the infant than the manufacturer’s recommendations. In infants whose TSB concentration is approaching the exchange transfusion threshold, the addition of a fibre optic blanket under the infant can increase the surface area illuminated, and the diaper should then be removed (or a phototherapy wavelength-transmitting diaper used instead). The entry criteria for each of these studies differed, making exact treatment indications difficult to determine.
Supplemental fluids are indicated, and IVIG should be given if not already commenced for the infant with isoimmunization. Appropriate amounts of blood should be taken and stored for tests such as those for red cell fragility, enzyme deficiency (G6PD or pyruvate kinase deficiency) and metabolic disorders, as well as for hemoglobin electrophoresis and chromosome analysis.
Infants with isoimmunization are at risk for severe anemia after several weeks; it is suggested that a repeat hemoglobin measurement be performed at two weeks if it was low at discharge and at four weeks if it was normal (evidence level 5). 65 (Prepared by Tufts-New England Medical Center Evidence-based Practice Center under Contract No.


If we assume that the entire 20% of infants with neurological findings at presentation had acute bilirubin encephalopathy, the incidence of this complication would be one in 10,000 live births, an incidence similar to that of phenylketonuria.
This may represent cultural differences in the approach to breastfeeding and the support mechanisms in place. The reference lists of recent publications were also examined – in particular, the evidence-based review by Ip et al [16] and a more extensive review by the same author [12] performed for the Agency for Healthcare Research and Quality of the US Department of Health and Human Services. Finally, when the TSB concentration was above the 75th percentile, 12.9% of infants subsequently exceeded the 95th percentile [9].
Testing all babies whose mothers are group O does not improve outcomes compared with testing only those with clinical jaundice [35][36] (evidence level 2b). G6PD deficiency increases the likelihood of requiring exchange transfusion in infants with severe hyperbilirubinemia; therefore, a test for G6PD deficiency should be considered in all infants with severe hyperbilirubinemia (evidence level 5). There is an opportunity to perform universal screening for either TSB or transcutaneous bilirubin (TcB) before the period of highest risk [19][42] and to use this to determine the risk profile and individualize follow-up.
Systems to ensure follow-up within the recommended intervals after hospital discharge must be in place so that an infant who develops severe hyperbilirubinemia can be identified and treated promptly. However, the results are more accurate at lower levels of bilirubin, and therefore, use of TcB as a screening device is reasonable [46]. Infants who lose more than 10% of their birth weight should be carefully evaluated by an individual with training and experience in support of breastfeeding mothers [64][65] (evidence level 5).
Side effects of phototherapy include temperature instability, intestinal hypermotility, diarrhea, interference with maternal-infant interaction and, rarely, bronze discolouration of the skin [41]. The guidelines for therapy (Figure 2) are based on limited direct evidence, but the Canadian Paediatric Society’s Fetus and Newborn Committee believed that the consensus of the American Academy of Pediatrics’ Subcommittee on Hyperbilirubinemia was the most appropriate currently available standard [20]. It appears reasonable to initiate this treatment in infants with predicted severe disease based on antenatal investigation and in those with an elevated risk of needing exchange transfusion based on the postnatal progression of TSB concentration. Preparation of blood for exchange transfusion may take several hours, during which time intensive phototherapy, supplemental fluids and IVIG (in case of isoimmunization) should be used.
Infants requiring exchange transfusion or those who exhibit neurological abnormalities should be referred to regional multidisciplinary follow-up programs. Sensitivity and specificity were calculated for each of the values of the OGTT as a diagnostic test, with the gold standard being perinatal outcome.ResultsThe most frequent risk factors were obesity, arterial hypertension and advanced maternal age. Blood glucose values were measured at the age of 1 h, 6 h, 12 h, 24 h and 48 h after delivery which was independent of feeding time. Prognosis of these newborns with hypoglycemia depends on how promptly and efficiently hypoglycemia is managed. The incidence of chronic encephalopathy is also uncertain, but it has been estimated to be approximately one in 100,000 [19][20]. The references of the recent statement of the American Academy of Pediatrics [11] were also examined.
Therefore, it is reasonable to perform a DAT in clinically jaundiced infants of mothers who are group O and in infants with an elevated risk of needing therapy (ie, in the high-intermediate zone [Figure 1]). It should also be recognized that in the presence of hemolysis, G6PD levels can be overestimated and this may obscure the diagnosis [40].
Furthermore, clinical assessment of jaundice is inadequate for diagnosing hyperbilirubinemia. This requires, for example, that an infant discharged from hospital in the first 24 h of life be reviewed within 24 h, any day of the week, by an individual with the training to recognize neonatal hyperbilirubinemia, obtain measurement of TSB or TcB without delay and refer the infant to a treatment facility if required. The available devices differ in accuracy; safe use of the device mandates knowledge of the accuracy of the particular device. Routine supplementation of breastfed infants with water or dextrose water does not appear to prevent hyperbilirubinemia (evidence level 2b) [66]. Phototherapy in the neonatal period is perceived by parents as implying that their infant’s jaundice was a serious disease [78], and is associated with increased anxiety and health care use (evidence level 2).
Conventional phototherapy – a single bank of fluorescent lights placed above the incubator of an infant nursed with a diaper in place – is, of course, less effective because both surface area and intensity are reduced; nevertheless, it will have an effect on TSB concentration.
If an infant whose TSB concentration is already above the exchange transfusion line presents for medical care, then repeat measurement of the TSB concentration just before performance of the exchange is reasonable, as long as therapy is not thereby delayed. Neurosensory hearing loss is of particular importance in infants with severe hyperbilirubinemia, and their hearing screen should include brainstem auditory evoked potentials. The most common neonatal outcomes were large-for-gestational-age infants, Cesarean delivery and preterm birth. The maintenance of normoglycemia in newborns depends upon adequacy of glycogen stores, maturation of glycogenolytic and gluconeogenic pathways and an integrated endocrine response.
All of the reasons for the variable susceptibility of infants are not known; however, dehydration, hyperosmolarity, respiratory distress, hydrops, prematurity, acidosis, hypoalbuminemia, hypoxia and seizures are said to increase the risk of acute encephalopathy in the presence of severe hyperbilirubinemia [9][11], although reliable evidence to confirm these associations is lacking [12]. This situation occurs despite the fact that a large number of infants already receive intensive preventive therapy [11]. The results will determine whether they are low risk or high risk, and may therefore affect the threshold at which therapy would be indicated (Figure 2).
Reassurance of the parents that appropriate intervention and follow-up will prevent any consequences of hyperbilirubinemia is an important part of the care of these infants. Sick newborns, those less than 34 weeks of gestation or less than 1500 g, infant of diabetic mother, those with birth asphyxia, congenital malformations and endocrine deficiencies were excluded.
In addition, some infants with severe hyperbilirubinemia are found to have sepsis, but both sepsis and hyperbilirubinemia are common in the neonatal period, and sepsis appears to be uncommon in the well-appearing infant with severe hyperbilirubinemia. The CPSP report [18] noted that 13 of the infants continued to have important neurological abnormalities at final discharge, suggesting a chronic bilirubin encephalopathy incidence of one in 50,000, similar to the frequency reported from a Danish study [21].
G6PD-deficient newborns may require intervention at a lower TSB concentration because they are more likely to progress to severe hyperbilirubinemia [42][43]. Eye patches should be used to protect the developing retina because animal studies demonstrate a potential risk [79]. Exchange transfusion is a procedure with substantial morbidity that should only be performed in centres with the appropriate expertise under supervision of an experienced neonatologist. Rockville, MD: US Department of Health and Human Services, Agency for Healthcare Research and Quality, 2003. Unfortunately, in many centres, it currently takes several days for a G6PD deficiency screening test result to become available. An infant with clinical signs of acute bilirubin encephalopathy should have an immediate exchange transfusion (evidence level 4). GDM is diagnosed when two or more values are found to be above the established cut-off limits.
Usually the transition from intra-uterine glucose regulation to extra-uterine adaptation develops in first 24 h of age.
Although there have been no prospective, controlled trials to evaluate the effectiveness or cost-benefit relationship of universal screening, it appears to be a reasonable strategy, and an observational study [46] has reported it to be effective (evidence level 4). These recommendations were based on studies conducted by O'Sullivan and Mahan, published in 1964 [2] and adapted by Carpenter and Coustan in 1982 [3]. Because G6PD deficiency is a disease with lifelong implications, testing infants at risk is still of value.
They have been maintained for the past 10 years [4].The International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommended the adoption of certain markers for screening. According to the guidelines proposed by IADPSG, only one value above the cut-off limit in the 3-hour OGTT is sufficient to justify a diagnosis of GDM. If applied, this criterion will lead to a diagnosis of GDM in 18-20% of the entire obstetric population [5].In parallel, a diabetes study group in Brazil developed a consensus statement on the diagnosis and treatment of diabetes in pregnancy. This consensus established the 2-hour OGTT with 75 g of dextrosol as the standard diagnostic test, with a diagnosis of GDM being established when at least two values are above the cut-off limits, which coincide with those of the ADA proposal [4a€“6].The thresholds adopted by the ADA for the 3-hour OGTT are useful for diagnostic purposes in populations similar to that of Brazil in which the prevalence of GDM is moderate when compared to other, previously tested populations such as those of certain European countries and the United States.
The results established in those populations formed the basis for defining the current cut-off limits [4].Screening, however, is still carried out based on the presence of risk factors and by measuring fasting blood glucose levels. An additional objective was to assess the accuracy of the OGTT for the prediction of adverse perinatal outcomes in this same population.MethodsA study was conducted to validate a diagnostic test (3-hour OGTT) in pregnant women who had screened positive for GDM but who had a normal 3-hour, 100-gram OGTT.
The terms "AGA" and "SGA" were defined according to intrauterine growth curves based on percentile of birth weight.
Pinotti Women's Hospital, a teaching hospital at the State University of Campinas (UNICAMP), between January 2000 and December 2009.Sample size was calculated at 400 tests from 400 pregnant women. For infants delivered by cesarean section (CS), breastfeeding was started as soon as feasible and maximum within 4 h of delivery.
The inclusion criteria consisted of a positive screening test for diabetes mellitus and an OGTT with either only one value above the cut-off level or with all values within the normal range (e.g.
Based on BFHI, 24 h rooming in and kangaroo mother care is practiced to encourage breast feeding.
Newborns are separated from mother only in cases of maternal illness and until she is transferred to the ward.
Of the remaining 2,348 tests, 1,123 women received a diagnosis of gestational diabetes mellitus. With respect to the other 1,225 OGTT performed, 803 referred to women who had undergone prenatal care or had delivered their infant at another clinic. Of the remaining 422 tests, criteria for diagnosis were present in 10 cases, while 412 were considered normal. By observing the trends of deliveries conducted in our hospital over the past two years, we assumed 80% of newborns to be AGA and 20% to be SGA.
Receiver operating characteristic curves (ROC) were constructed for the OGTT as a diagnostic test, with the gold standard being the perinatal variables. The area under the ROC curve was considered statistically significant when it differed by 50%. Of these, three were infants of diabetic mother, four had birth asphyxia and two had congenital malformation. Capillary blood was collected by heel prick after proper aseptic measure for screening by reagent strips method and the same time venous blood sample was sent for laboratory confirmation by glucose oxidase method in an autoanalyzer. Lethargy, jitteriness and seizures, tremor, apnea, poor feeding etc were considered to be clinical signs of hypoglycemia if they were unexplained by other diagnoses and corrected with the provision of glucose.
Another important risk factor was chronic hypertension (23%), followed by maternal age (20%) and a family history of diabetes (20%). Infants were considered as asymptomatic if low plasma glucose concentration was not associated with clinical signs. Thirty-seven percent of the women had only one risk factor, while around one-third had two or more risk factors. Infants found to have hypoglycemia were clinically re-examined, given an additional breast-feed and plasma glucose reassessed after 30 min. Fasting blood glucose level was abnormal in about 10-12% of the women; however, this constituted the only risk factor in less than 2% of patients. Five newborn developed early onset septicemia and two were later found to have hypoglycemia secondary to metabolic causes. During the study, ethical issues were dealt rigorously according to revised Helsinki 2000 protocol. These data are in agreement with reports published in the medical literature over the years [7, 8].Abnormal fasting blood glucose levels were not a relevant indication for performing an OGTT. Prior to enrollment in the present study, parents and responsible caregivers of the neonates were properly counseled in their own vernacular and a written informed consent was taken from them.Statistical analysisData were presented in the form of statistical Tables and charts. This finding contradicts what has been established in the literature in which this is highlighted as constituting a basic parameter [9]. However, when blood glucose is associated with a risk factor, it gains importance as an indication for performing an OGTT [10, 11]. It should be emphasized that clinical signs during pregnancy such as maternal weight gain, fetal weight and increased amniotic fluid are strongly related to glucose intolerance and should signal a need to request an OGTT. To construct these ROC curves, cumulative numbers were used that focused on one extreme, generally the lower limits, and with this technique the cut- off limit is shifted to lower numbers.Another limitation of the study was the fact that neonatal variables were used as the gold standards, and these are likely to be affected by several other factors, unlike the markers that have been used specifically for GDM and dysglycemia such as cord blood C-peptide and the percentage of body fat in the neonate [14]. By linear regression analysis, the effect of individual variables on hypoglycemia was assessed.
These markers are highly specific for GDM and metabolic disturbances, and are used to identify pregnant women in whom metabolic changes are minimal [15].
However, in terms of perinatal care in developing countries where resources are sparse, this strategy of placing the emphasis on clinical data appears extremely timely and useful.Naturally, in studies involving larger samples such as the HAPO study, values other than those obtained in the present study may be found.



Can low glucose levels cause seizures
Normal glucose level for 2 year old 7'4


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