William B. Pittard

Osteocalcin, Skeletal Alkaline Phosphatase, and Bone Mineral Content in Very Low Birth Weight Infants: A Longitudinal Assessment

Serum osteocalcin (Gla) and skeletal alkaline phosphatase (SAP) concentration both reflect osteoblast activity in the dynamic process of bone formation. To assess the relation in premature infants between change in bone mineral content (BMC) and both Gla and SAP serum concentration, we longitudinally measured BMC via photon absorptiometry and serum Gla and SAP concentration from birth to 16 wk in 20 very low birth weight infants. Serum total calcium, phosphorus, parathyroid hormone, and vitamin D metabolite concentrations were also monitored. All serum values were measured in the 20 mothers at delivery. Cord blood Gla concentrations were significantly (p < 0.03) greater than maternal levels, and by 1 wk had significantly (p < 0.001) increased from birth values. Total calcium, parathyroid hormone, phosphorus, and vitamin D concentrations remained in the normal range throughout the study. The increase in serum Gla concentrations, birth to 1 wk, were significantly correlated with the simultaneous increase in 1, 25-dihydroxyvitamin D concentrations. The correlation between the change in BMC, however, over the first 4 mo of life and both Gla and SAP serum concentrations failed to reach statistical significance. Finally, a significant (p < 0.003) negative correlation was measured between serum Gla and SAP concentrations at wk 4, and, although not significant, a consistently negative correlation was measured from 1–16 wk of age. These data demonstrate a 1, 25-dihydroxyvitamin D associated rise in neonatal serum Gla concentration during the 1st week after delivery, no significant correlation between the change in neonatal BMC over the first 4 mo of life and serum Gla or SAP concentration, and a consistent negative correlation between serum Gla and SAP concentrations. These data do not indicate that either serum Gla or SAP concentration is a reliable predictor for the change in bone mineral content of very low birth weight infants over the first 16 wk of life.

Newborn hospitalization: A closer look

To assess the safety of moderately early hospital discharge for normal newborn Infants (mean ±SD, 31±5 hours after delivery), we compared the incidence of hospital readmission within 6 weeks of birth with the incidence of readmission among a simllar cohort of infants with extended hospitalization (mean±SD, 92±44 hours) as a result of maternal illness. The hospital charts for all infants admitted to the well-baby nursery between January 1 and December 31, 1985, were reviewed. Fifty-two (3.0%) of the 1714 infants who were discharged moderately early and 17 (2.7%) of the 622 infants who had an extended hospitalization were readmitted to the hospital by age 6 weeks (P=NS). Matenral age, financial status, and race each failed to predict infant readmission. Only four of the 52 readmission diagnoses among infants discharged moderately early could potentially have been identified (not prevented) before discharge with an extended newborn hospitalization. These data indicate that moderately early neonatal hospital discharge does not result in an increased incidence of rehospitalization within the first 6 weeks of life.

Variation in the Biochemical Forms of Transforming Growth Factor-α Present in Human Milk and Secreted by Human Milk Macrophages

OBJECTIVE Transforming growth factor-alpha (TGF-alpha), present in human milk, is thought to play a significant role in postnatal gut development. Macrophages, which abound in human milk, are known to secrete various isoforms of TGF-alpha in other areas of the body. It was hypothesized that human milk macrophages (HMM) secrete TGF-alpha, and HMM are a source of TGF-alpha isoforms present in human milk. We sought to measure in vitro HMM TGF-alpha secretion, and to compare the TGF-alpha isoform(s) present in human milk with those secreted by HMM. STUDY DESIGN Colostrum and mature milk samples, obtained from mothers (n = 48) on postpartum days 3-30, were centrifuged. HMM were isolated, placed in culture for 24 h, and cell-free media collected. The biochemical forms of TGF-alpha in media in human milk supernatant samples were identified by Western blot analysis under reducing conditions. The concentration of the mature (6-kD) TGF-alpha isoform in those samples was quantified using a radioimmunoassay. RESULTS Western blot analysis under reducing conditions identified a single 6-kD TGF-alpha isoform in all human milk supernatant samples tested, but variable (6- and 30- to 46-kD) TGF-alpha isoforms in HMM media. The mean (+/- SE) concentration of the 6-kD TGF-alpha isoform found in human milk supernatants was 706 +/- 88 pg/ml and 17.6 +/- 2.6 pg/ml in HMM media. CONCLUSION These experiments show that HMM secrete TGF-alpha in biochemical forms both similar to and distinct from that found in human milk supernatant.

Cord Blood Amino Acid Concentrations from Neonates of 23—41 Weeks Gestational Age

Amino acid concentrations were measured in the cord blood serum from neonates following 23-41 weeks gestation. These values were then correlated with the gestational age of the newborns. A significant (p less than 0.05) correlation was observed with the concentrations of six amino acids, and five of these correlations were negative. The significance of these normative data are discussed and compared with currently available cord blood aminogram data.

NEWBORN HOSPITALIZATION: A CLOSER LOOK

To assess the safety of early newborn hospital discharge (mean ± SD, 32 ± 6 hours post delivery), among 808 well newborn infants, the incidence of hospital read-mission within 6 weeks of birth was determined. This incidence was then compared to the incidence of readmission among a similar cohort (n=284) of well infants assigned prolonged newborn hospitalization (mean + SD, 103 ± 54 hours) for maternal reasons. The hospital charts for all newborns admitted to the well baby nursery between January 1 and June 30, 1985 were reviewed. Twenty-two of the 808 (2.7%) early discharge infants and 8 of the 284 (2.8%) extended hospitalization infants were readmitted to the hospital by age six weeks. These readmission rates were not significantly (p=ns) different. Maternal age, financial status, and race each failed to predict infant readmission. Only two of the 22 readmission diagnoses observed among early discharged newborns potentially could have been identified (not prevented) prior to discharge with an extended newborn hospitalization. These data indicate that early neonatal hospital discharge does not result in an increased incidence of rehospitalization within the first six weeks of life.

A new method to examine very low birth weight fetal and hebdomadal mortality in a regionalized system of perinatal care.

Objective: Aggressive maternal transport of very low birth weight (VLBW) live births from community hospitals to regional perinatal centers may artificially increase community fetal death rates. By allocating maternal transports according to the location of antepartum and intrapartum care and separately computing antepartum and intrapartum fetal mortality rates, a more appropriate measure of hospital-based mortality may be determined. Method: Delivery charts were reviewed for 568 VLBW deliveries (including 97 fetal deaths and 77 hebdomadal deaths) occurring between 1990 and 1992 in a geographically defined perinatal region. Maternal transports were analyzed with community hospitals for antepartum mortality rates and with the regional center for intrapartum mortality rates. Results: Using traditional methods, the fetal mortality rates for community hospitals and the regional center were antepartum 385.1 vs. 45.2, respectively, and intrapartum 120.9 vs. 24.9, respectively. When regional center live births (maternal transports) are placed with community hospitals for analysis of antepartum mortality, the new antepartum mortality rates were 185.7 vs. 72.8, respectively. The hebdomadal mortality rate for community hospitals was 250.0 as compared to 145.8 for the regional center. Conclusion: Maternal transports to a regional center represent successful antepartum management by community care providers. Even though they delivered in the regional center, they should be analyzed with community hospitals for antepartum fetal mortality comparisons. Therefore, antepartum and intrapartum fetal mortality should be examined separately in a functioning regionalized perinatal care program where the location of patient care differs from location of delivery.

The immunologic composition of neonatal milk: cellular components.

The cellular content of neonatal mammary gland secretions from 12 full-term infants less than 2 weeks postdelivery was studied. The predominant cell types observed were lymphocytes and macrophages with greater than 90% viability in each. The concentration of lymphocytes was significantly (P less than 0.001) correlated with the concentration of macrophages. The immunoglobulin content of this fluid was predominantly IgG with minimal concentrations of IgA, and no IgM detected. These data suggest both the presence of regulatory mechanisms for the cellular composition of neonatal breast secretions and that neonatal milk may bear a significant connection with the developing mucosal immune system.

School Readiness Among Children Insured by Medicaid, South Carolina

Introduction The American Academy of Pediatrics recommends a schedule of age-specific well-child visits through age 21 years. For children insured by Medicaid, these visits are called Early and Periodic Screening, Diagnosis, and Treatment (EPSDT). These visits are designed to promote physical, emotional, and cognitive health. Six visits are recommended for the first year of life, 3 for the second year. We hypothesized that children with the recommended visits in the first 2 years of life would be more likely than others to be ready for school when they finish kindergarten. Methods We studied children insured by Medicaid in South Carolina, born during 2000 through 2002 (n = 21,998). Measures included the number of EPSDT visits in the first 2 years of life and an assessment of school readiness conducted at the end of kindergarten. We used logistic regression to examine the adjusted association between having the recommended visits and school readiness, controlling for characteristics of mothers, infants, prenatal care and delivery, and residence area. Results Children with the recommended visits had 23% higher adjusted odds of being ready for school than those with fewer visits. Conclusion EPSDT may contribute to school readiness for children insured by Medicaid. Children having fewer than the recommended EPSDT visits may benefit from school readiness programs.

URINARY SODIUM/POTASSIUM RATIO AS A MARKER FOR SERUM ATRIAL NATRIURETIC PEPTIDE (ANP) LEVELS. 2187

Newborns undergo an isotonic contraction of their extracellular fluid (ECF) volume in the first days of life. This is reported to be secondary to a sodium diuresis proportional to the serum ANP level. To determine if the postnatal urine sodium/potassium ratio can be used as a marker in VLBW infants for plasma ANP levels, eleven babies without sepsis or history of asphyxia were studied. Their mean ± SD BW and GA was 1284 ± 145 g and 29.8± 1.1 wks, respectively. Serum and spot urine, sodium, potassium and creatinine and serum ANP levels were determined on day 4,7,10,14 and 19 of life. Sodium and potassium values were determined via routine potentiometric methodology. Creatinine was determined enzymatically with Kodak Ektachem slides. ANP was determined via RIA. Daily weight as well as total volume and sodium intake were recorded. The mean ± SD ANP levels fell from 47.58± 31.1 pg/ml on day 4 to 37.7 ± 36.7 pg/ml on day 10 with little further change through day 19. The mean ± SD fractional sodium excretion fell from 3.5 ± 2.3% on day 4 to 0.74 ± 0.6% on day 10 and remained < 1.0% thereafter. The mean ± SD urine sodium/potassium ratio fell from 5.49 ± 2.56 on day 4 to 1.25 ± 1.11 on day 10 with little further change through day 19. Serum ANP levels significantly(p<.02) correlated with fractional sodium excretion. Further, the ANP values were significantly (<.01) correlated with the log of urine sodium/potassium ratio but not with total volume or sodium intake/day. We conclude that serum ANP concentrations correlate directly in VLBW infants with renal sodium regulation. Similarly, the log urine sodium/potassium ratio can be used as a predictor of serum ANP levels.

Calcium homeostasis and its relationship to bone disease in the human neonate

Although the study of calcium homeostasis and a clear understanding of its physiologic pathways in neonates have evolved more slowly than in older children and adults, greater strides have been made in recent years to expand this area of study. Similarly, the identification, examination, and etiologic understanding of neonatal osteopenia (rickets of prematurity) and its relationship with calcium homeostasis have been examined. This paper reviews the current literature on neonatal calcium homeostasis and the development of neonatal osteopenia, perhaps the most common bone disease of prematurity.