Hepatic involvement in perinatal asphyxia.

BACKGROUND: The pathogenetic mechanisms of hepatic injury in perinatal asphyxia (PNA) are similar to those in ischemic hepatitis, yet liver involvement is currently not considered a component of multi-organ failure in PNA. METHODS: A retrospective study was done on 56 newborns with PNA. Hepatocyte injury was diagnosed based on elevated serum alanine transaminase level (>100 U/L, twice upper normal) with subsequent normalization. RESULTS AND CONCLUSIONS: Twenty-two of the patients had hepatocyte injury. Fetal distress, thrombocytopenia, convulsions, pathologic findings on imaging of the central nervous system, and a high rate of intrauterine growth retardation were the factors significantly associated with hepatocyte injury. This damage was also associated with high mortality.

Effect of feeding type on the efficacy of phototherapy.

OBJECTIVE: The objective of this study was to assess the efficacy of phototherapy for nonhemolytic hyperbilirubinemia and rebound bilirubin levels in breast-fed newborns as compared with mixed-fed (breast milk and formula) newborns. STUDY DESIGN/SETTING: Prospective study of effects of feeding type on response to phototherapy in newborns. METHODS: The subjects were 53 full-term healthy newborns with nonhemolytic hyperbilirubinemia [defined as total serum bilirubin 12 mg/dL (205.2 micromol/L) in the first 48 hours of life or 15 mg/dl (256.5 micromol/L), on subsequent days]. Groups were formed according to type of feeding. Group 1 consisted of 28 breast-fed newborns and group 2 consisted of 25 mixed-fed newborns. Phototherapy was terminated when total serum bilirubin concentration fell to 14 mg/dL (< 239.4 micromol/L). Rebound bilirubin measurements were obtained 24 hours after phototherapy ended. RESULTS: The groups were comparable with respect to age at the start of phototherapy. The amount of weight loss (relative to birth weight) recorded at the start of phototherapy was significantly greater in group 1 than in group 2 (8.1+/- 3.9% vs. 5.4+/- 2.6% p = 0.004). The duration of phototherapy was significantly longer in group 1 than in group 2 (38.6+/- 12.6 h vs. 26.8+/- 9.4 h; P < 0.001). The 24-hour rate of decrease in bilirubin concentration in group 2 was significantly higher than that in group 1 [5.4+/- 2.2 mg/dL/d (92.3+/-37.6 micromol/L/d) vs. 4+/- 1.3 mg/dL/d (68.4+/- 22.2 micromol/L/d); p = 0.01]. The overall rate of decrease in bilirubin concentration in group 1 was significantly lower than that in group 2 [0.16+/- 0.05 mg/dL/h (2.73+/- 0.85 micromol/L/h) vs. 0.22+/- 0.09 mg/dL/h (3.76+/- 1.53 micromol/L/h); p = 0.01]. There was no significant difference between the two groups with respect to rebound bilirubin concentration (P = 0.184). CONCLUSION: Phototherapy effectively reduced bilirubin levels in breastfed newborns with hyperbilirubinemia, but these patients show significantly slower response to this treatment than mixed-fed newborns.

Early onset conjugated hyperbilirubinemia in newborn infants.

OBJECTIVES: To determine the causes and related outcomes of early onset conjugated hyperbilirubinemia in a group of newborn infants and to determine the incidence of sepsis in these neonates. METHODS: The charts of 42 babies with conjugated hyperbilirubinemia were retrospectively reviewed. RESULTS: The mean gestational age was 37 weeks and the mean postnatal age at presentation was 10 days. Culture-proven sepsis was identified in 15 babies (35.7% of total). Gram-negative bacteria were isolated in 10 cases and E. coli was the most common of these agents (7 cases). Perinatal hypoxia-ischemia was the second most frequent etiology (7 patients; 16.7% of total). The other diagnoses were blood group incompatibility (n=5), Down syndrome (n=3), cholestasis associated with parenteral nutrition (n=3), neonatal hepatitis (n=2), metabolic liver disease (n=1), biliary atresia (n=1), portal venous thrombosis (n=1) and unknown (n=4). Thirteen babies with sepsis recovered completely with treatment, whereas the prognosis for those with perinatal hypoxia-ischemia was grave (six of seven died). CONCLUSIONS: The findings suggest that early onset cholestatic jaundice in newborn infants is more commonly from non-hepatic causes, so it is reasonable to monitor these infants carefully for a period of time before undertaking time-consuming or invasive investigations towards a primary liver disease.

Extreme hyperbilirubinemia in newborn infants.

This study was undertaken to determine the frequency and investigate the etiology of extreme hyperbilirubinemia (total serum bilirubin [TSB]>or=25 mg/dL [428 micromol/L]) in newborns admitted to a neonatal intensive care unit in southern Turkey. The charts of 93 term and near-term infants admitted with TSB levels of 25 mg/dL (428 micromol/L) or greater in the first 30 days after birth were retrospectively reviewed. During the 4.5-year study period, 774 infants were admitted to our unit with neonatal jaundice. Ninety-three (12%) of these infants had TSB levels of 25 mg/dL (428 micromol/L) or greater. The mean TSB level in the 93 cases was 30.1+/-5.7 mg/dL (514.7+/-97.5 micromol/L), and the peak levels ranged from 25.0 to 57.4 mg/dL (428-981.5 micromol/L). Thirty-three (35.5%) of the 93 babies had TSB levels of 30 mg/dL (513 micromol/L) or greater. Eighty-nine of 93 infants were being exclusively breast-fed. Nineteen babies were isoimmunized, 7 were bacteremic, 2 of the 39 babies tested for glucose-6-phosphate dehydrogenase had this enzyme deficiency, and 1 of the 71 infants tested for thyroid function had hypothyroidism. No cause for extreme hyperbilirubinemia was found in 61 (65.6%) cases.

Serum pro-hepcidin levels and relationships with iron parameters in healthy preterm and term newborns.

A recently isolated peptide hormone, hepcidin, is thought to be the principal regulator of iron homeostasis. Hepcidin acts by limiting intestinal iron absorption and promoting iron retention in reticuloendothelial cells. Its precursor peptide form is called pro-hepcidin. The aims of this study were to determine serum pro-hepcidin levels in healthy preterm and term newborns, and to assess possible relationships between pro-hepcidin and serum iron, serum ferritin, and transferrin. A serum sample was collected from each of 26 healthy preterm (gestational age < 37 weeks) and 16 healthy, full-term, appropriate-for-gestational age babies. The preterm babies were also divided into 2 subgroups based on gestational age. Samples were analyzed for complete blood count, serum iron and ferritin concentrations, iron-binding capacity, and transferrin and pro-hepcidin levels. Group findings were compared and correlations between pro-hepcidin and the iron parameters were tested. The respective serum pro-hepcidin levels (mean +/- SD) in the 16 healthy term and 26 healthy preterm newborns were 482 +/- 371.9 ng/mL and 496.7 +/- 443.5 ng/mL. Analysis revealed no significant correlations between serum pro-hepcidin level and serum iron, serum ferritin, or transferrin in the preterm or term newborns. Pro-hepcidin levels were not correlated with gestational age in the preterm group. The results indicate that healthy preterm and term newborns have high pro-hepcidin levels.

Role of HOXA7 to HOXA13 and PBX1 genes in various forms of MRKH syndrome (congenital absence of uterus and vagina).

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome refers to the congenital absence or severe hypoplasia of the female genital tract, often described as uterovaginal aplasia which is the prime feature of the syndrome. It is the second cause of primary amenorrhea after gonadal dysgenesis and occurs in approximately 1 in 4500 women. Aetiology of this syndrome remains poorly understood. Frequent association of other malformations with the MRKH syndrome, involving kidneys, skeleton and ears, suggests the involvement of major developmental genes such as those of the HOX family. Indeed mammalian HOX genes are well known for their crucial role during embryogenesis, particularly in axial skeleton, hindbrain and limb development. More recently, their involvement in organogenesis has been demonstrated notably during urogenital differentiation. Although null mutations of HOX genes in animal models do not lead to MRKH-like phenotypes, dominant mutations in their coding sequences or aberrant expression due to mutated regulatory regions could well account for it. Sequence analysis of coding regions of HOX candidate genes and of PBX1, a likely HOX cofactor during Müllerian duct differentiation and kidney morphogenesis, did not reveal any mutation in patients showing various forms of MRKH syndrome. This tends to show that HOX genes are not involved in MRKH syndrome. However it does not exclude that other mechanisms leading to HOX dysfunction may account for the syndrome.

Fatal course of ABO hemolytic disease associated with hydrops in a twin pregnancy.

Hydrops fetalis associated with ABO incompatibility is an extremely rare condition. We report twin infants both afflicted with significant ABO hemolytic disease but showing different degrees of clinical severity, in which fatal hydrops developed in one of the twins. Hemolysis due to ABO incompatibility is usually difficult to diagnose. All causes of non-immune hydrops should be ruled out in order to identify hydrops due to ABO incompatibility.

Effect of perinatal factors on time of first stool passage in preterm newborns: An open, prospective study.

BACKGROUND: Delayed passage of first stool by a newborn after birth might be an initial sign of clinical problems, such as meconium ileus, meconium plug syndrome, and intestinal atresia. Successful treatment of these conditions depends on early diagnosis, so it is imperative to note the time of first stool passage. OBJECTIVE: The aim of this study was to assess the timing of first stool passage by preterm newborns in relation to antenatal exposure to magnesium sulfate (MgSO4) and a glucocorticoid (betamethasone) and to other perinatal factors, such as gestational age, respiratory distress syndrome (RDS), and time of first enteral feeding. METHODS: The subjects in this prospective, open study were preterm newbornswho were born before 37 weeks' gestation and admitted to the neonatal intensive care units of Baskent University, Adana Teaching and Research Center, and Inonu University, Turgut Ozal Medical Center, between June 2003 and August 2004. Effects of antenatal exposure to MgSO4 and glucocorticoid on the timing of first stool passage were assessed by comparing findings in exposed newborns to findings in an equal-sized group of gestational-age-matched subjects, derived from the study cohort, who were not exposed. Relationships between time of first stool passage and both gestational age and time of first enteral feeding were assessed. RESULTS: Two hundred premature newborns (112 males, 88 females) were included in the study. The median age at the time of first stool passage was 16 hours, and 187 (93.5%) passed their first stool by 72 hours after birth. Delayed passage of first stool was noted in 33 (16.5%) newborns. One hundred sixty-eight (84.0%) newborns passed stool before enteral feeding was started. Gestational age and time to first enteral feeding were both significantly correlated with time of first stool passage (gestational age: r = -0.259, P < 0.001; first enteral feeding: r = 0.168, P = 0.017). Time of first stool passage was significantly later in 46 newborns with RDS than in 46 gestation al-age-matched newborns without RDS (mean [SD], 44.7 [39.7] vs 20.5 [18.4] hours, respectively; P < 0.05). The newborns whose mothers had received MgSO4 for tocolysis passed their first stool significantly later than gestational-age-matched controls (mean [SD], 26.5 [26.9] vs 11.3 [12.1] hours, respectively; P < 0.05). Antenatal exposure to betamethasone was not significantly correlated with timing of first stool passage. CONCLUSIONS: The results suggest that delayed passage of first stool in thesepreterm newborns was associated with gestational immaturity, delayed first enteral feeding, and RDS. Antenatal maternal exposure to MgSO4 was associated with later first stool passage in these preterm newborns, whereas antenatal exposure to betamethasone was not.

Weight loss and hypernatremia in breast-fed babies: frequency in neonates with non-hemolytic jaundice.

OBJECTIVE: The aim of this study was to determine what proportion of newborns admitted with idiopathic non-hemolytic hyperbilirubinemia exhibit severe weight loss and hypernatremia. METHODS: The prospective study involved 115 infants >48 h old who were admitted with jaundice between July 2002 and July 2003, and had unconjugated bilirubin levels >12 mg/dL. Premature babies (gestational age <37 weeks) and those with hemolytic jaundice and other pathologic causes of non-hemolytic jaundice were excluded. Postnatal age (days) at admission, bodyweight at admission, weight change since birth (percentage weight loss calculated at admission) and mode of feeding (breast-feeding, formula feeding, mixed feeding) were recorded. Severe weight loss was defined in babies who showed >10% weight loss or had not regained enough to reach birthweight by postnatal day 10. Serum Na levels and breast-milk Na levels were also measured. RESULTS: Twenty-eight (33%) of the 86 newborns with idiopathic hyperbilirubinemia in the study exhibited severe weight loss. Almost all the 86 babies were exclusively breast-fed, and 10 babies (12%) had severe weight loss combined with hypernatremia. The group with severe weight loss and hypernatremia had higher breast-milk Na levels than the other infants. CONCLUSION: The results indicate that a large proportion of babies with non-hemolytic jaundice have severe weight loss, and that breast-fed newborns with the combination of weight loss and hypernatremia may present with non-hemolytic jaundice.

Glycosaminoglycans in childhood urinary tract infections.

It has been suggested that urinary glycosaminoglycans (GAGs) form a natural defense mechanism against urinary tract infections (UTIs). This study investigated whether urinary GAGs play a role in pediatric UTIs, and whether urinary GAG level can be used to differentiate upper UTI from lower UTI. Forty-one children with UTIs (33 girls and eight boys; mean age 5.4+/-3.7 years) and 46 age- and sex-matched healthy children (35 girls and 11 boys; mean age 6.6+/-3.9 years) were included in the study. Urinary GAG levels were measured at the onset of acute infection and after a 10-day course of antibiotic treatment. Group GAG findings were compared, and comparisons were also made with the patients divided according to sex and according to UTI type (upper versus lower). The mean urinary GAG level in the patient group at the onset of acute infection (pretreatment) was significantly higher than the mean level in the control group (132.2+/-104.8 mg/g vs 42.2+/-27.1 mg/g creatinine, respectively; P <0.01). In the patient group, the mean urinary GAG level after antimicrobial therapy was significantly lower than the pretreatment level (75.9+/-52.1 mg/g vs 132.2+/-104.8 mg/g creatinine, respectively; P <0.01). However, the mean post-treatment level was still higher than the mean level in the controls ( P <0.05). There was no significant difference in urinary GAG levels when patients were categorized as upper versus lower UTI ( P >0.05). The study results suggest that GAGs play an important role in the pathogenesis of UTIs in children, and that measurement of urinary GAGs may be a valuable noninvasive method for evaluating UTIs in this patient group. However, this assay cannot be used to differentiate upper UTI from lower UTI in children.

Relationship between serum bilirubin and coagulation test results in 1-month-old infants.

OBJECTIVE: Although the connection between cholestasis and conjugated hyperbilirubinemia is well known, mild hepatic dysfunction or cholestasis may also be associated with unconjugated hyperbilirubinemia in some infants with prolonged jaundice. The aim of this study was to investigate the relationship between serum bilirubin levels and alanine aminotransferase levels, aspartate aminotransferase levels, prothrombin time, activated partial thromboplastin time, and international normalization ratio findings in a group of infants. METHODS: The study included 77 healthy, term, breast-fed infants with jaundice and 56 age-matched, healthy, term, non-jaundiced controls. The 133 babies were divided into three subgroups according to their total bilirubin levels [group I (controls) < 50 micromol/L, group II = 50-100 micromol/L, and group III > 100 micromol/L, and the findings for the noted parameters were compared]. RESULTS: The mean conjugated bilirubin level was significantly higher, and the mean activated partial thromboplastin time significantly longer in group III than in group I. A significant positive correlation was found between bilirubin levels and PT and APTT results. CONCLUSION: Clinical vitamin K deficiency appeared unlikely to develop in this group of infants with prolonged unconjugated hyperbilirubinemia. However, a significant positive correlation between bilirubin levels and PT and APTT suggest that a higher bilirubin load to the liver may cause some degree of vitamin K deficiency due to mild cholestasis. The importance of this finding, and the possible benefits of vitamin K supplementation in 1-month-old breast-fed infants with bilirubin levels higher than 100 micromol/L require further investigation.

Bilateral calcifications in the basal ganglia, and frontal and parietal lobes of a patient with coeliac disease.

Previous authors have described a specific syndrome of coeliac disease, bilateral cerebral calcifications and epileptic seizures. We report a 4-year-old boy with coeliac disease who had bilateral calcifications in the basal ganglia and frontal and parietal lobes, but did not exhibit epileptic seizures.

Relationship between serum bilirubin and coagulation test results in 1-month-old infants.

OBJECTIVE: Although the connection between cholestasis and conjugated hyperbilirubinemia is well known, mild hepatic dysfunction or cholestasis may also be associated with unconjugated hyperbilirubinemia in some infants with prolonged jaundice. The aim of this study was to investigate the relationship between serum bilirubin levels and alanine aminotransferase levels, asparte aminotransferase levels, prothrombin time, activated partial thromboplastin time and international normalization ratio findings in a group of infants. METHODS: The study included 77 healthy, term, breast-fed infants with jaundice and 56 age-matched, healthy, term, non-jaundiced controls. The 133 babies were divided into three subgroups according to their total bilirubin levels [group I (controls) <50 µmol/L, group II=50-100 µmol/L, and group III >100 µmol/L, and the findings for the noted parameters were compared]. RESULTS: The mean conjugated bilirubin level was significantly higher, and the mean activated partial thromboplastin time significantly longer in group III than in group I. A significant positive correlation was found between bilrubin levels and PT and APTT results. CONCLUSION: Clinical vitamin K deficiency appeared unlikely to develop in this group of infants with prolonged unconjugated hyperbilirubinemia. However, a significant positive correlation between bilirubin levels and PT and APTT suggest that a higher bilirubin load to the liver may cause some degree of vitamin K deficiency due to mild cholestasis. The importance of this finding, and the possible benefits of vitamin K supplementation in 1-month-old breast-fed infants with bilirubin levels higher than 100 µmol/L require further investigation.

Absent pulmonary valve syndrome diagnosed by fetal echocardiography.

Prenatal echocardiographic diagnosis of heart defects is important because it permits counseling of the parents with regard to prognosis and treatment options and prepares the medical team for the treatment postnatally. A male infant with absent pulmonary valve syndrome diagnosed prenatally at 22 weeks' gestation is reported. This congenital anomaly is characterized by absent or rudimentary pulmonary valve cusps, conoventricular septal defect, and massive dilatation of the pulmonary arteries. Soon after delivery the infant developed cyanosis and respiratory distress. The infant was placed in prone position for the relief of bronchial compression and nasal continuous positive airway pressure was (CPAP) started. Although the clinical status of the infant improved after supportive treatment, he deteriorated acutely and died at the age of five days. Fetal diagnosis remains an integral part of successful management of children with heart disease. Despite the potential benefits of prenatal diagnosis, it is hard to show significant improvement in mortality, especially in severely affected cases.

Influence of feeding formula and breast milk fortifier on lymphocyte subsets in very low birth weight premature newborns.

BACKGROUND: It is well known that breast-feeding protects the newborn from infectious diseases. This is especially important for very low birth weight preterm infants, whose immune systems are immature. In this study we investigated how a milk fortifier and replacement formula affected lymphocyte subsets in preterm infants. METHOD: The study assessed the effects of different types of feeding (human milk, n = 14; fortified human milk, n = 16; formula, n = 14) on lymphocyte subsets in 44 very low birth weight preterm infants. For each baby, two consecutive blood samples were collected 7-10 days apart during the full enteral feeding period. For each sample, the percentages of CD3+ (pan-T), CD19+ (B-cell), CD4+ (T-helper), CD8+ (T-suppressor), and CD3-CD16/56+ (natural killer cell) lymphocytes were measured in a flow cytometer, and the absolute count for each subset was calculated based on the total lymphocyte count. Within each feeding group, the absolute numbers of each lymphocyte subset in the two consecutive samples were compared. Also, the mean absolute counts for each cell type were compared among the 3 groups for the first set of blood samples, and the same comparisons were made for the second set. RESULTS: The mean number of CD3-CD16/56+ cells in the formula-fed infants was significantly lower than the corresponding means in the groups fed human milk alone and fortified human milk (p = 0.037). CONCLUSION: The findings suggest that babies fed formula have different lymphocyte subset compositions than those fed breast milk or fortified breast milk.

Serum bilirubin levels in 1-month-old, healthy, term infants from southern Turkey.

This study investigated bilirubin levels in 282 1-month-old, healthy, term infants from the Adana region in southern Turkey. Total bilirubin was > 5 mg/dl in 20.2% of the infants and > 10 mg/dl in 6% of the group. Thyroid function and levels of alanine aminotransferase, aspartate aminotransferase and glucose-6-phosphate dehydrogenase were determined in babies with bilirubin levels > 5 mg/dl. The results were normal in all but one case, an infant with a bilirubin level of > 10 mg/dl and glucose-6-phosphate dehydrogenase deficiency. The results indicate that in this population a 5-mg/dl cut-off level for further investigation would mean that 20% of all infants would require further evaluation. This is not cost-effective. Based on our findings, we suggest that the cut-off level for investigating prolonged jaundice in term, 1-month-old, healthy infants in the Turkish population should be > 5 mg/dl.