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Objective We describe five neonates with enteroviral (EV) infection to demonstrate central nervous system (CNS) and cardiac complications and report successful treatment of myocarditis with immunoglobulin intravenous (IVIG) in two. Study Design Case series identified during three enteroviral seasons in one neonatal intensive care unit (NICU) by cerebral spinal fluid (CSF) reverse transcriptase polymerase chain reaction (PCR) testing for EV in neonates suspected to have sepsis, but with sterile bacterial cultures. Results Cases were identified in each of three sequential years in a NICU with 800 to 900 admissions/year. Two cases were likely acquired perinatally; all were symptomatic with lethargy and poor feeding by age 5 to 10 days. All had signs of sepsis and/or meningitis; one progressed to periventricular leukomalacia and encephalomalacia. Two recovered from myocarditis after treatment that included IVIG 3 to 5 g/kg. Conclusion Neonates who appear septic without bacterial etiology may have EV CNS infections that can be diagnosed rapidly by CSF PCR testing. Cases may be underdiagnosed in the early neonatal period if specific testing is not performed. Neonates with EV infection should be investigated for evidence of periventricular leukomalacia, screened for myocarditis, and considered for IVIG treatment.

The high neonatal mortality rate in the United States relative to other developed countries is a national concern (Healthy People 2020 2010; World Health Organization 2010). The major clinical conditions associated with death in early infancy include premature birth; congenital malformation; sepsis; respiratory distress syndrome (RDS); necrotizing enterocolitis (NEC); hypoxia; intraventricular hemorrhage (IVH); and maternal conditions and complications involving the placenta, umbilical cord, and/or delivery (Guthrie et al. 2003; Shankaran et al. 2005; Heron et al. 2009). A system of regionalized perinatal care has evolved to deliver specialized care to high-risk obstetrical and neonatal patients (American Academy of Pediatrics Committee on the Fetus and Newborn 2012). However, in a voluntary system of regionalized perinatal care in which some patients are uninsured, health insurance status may affect access to neonatal intensive care and the neonatal mortality rate. Being uninsured is harmful to the health of older children and adults, and their health status may be improved by acquisition of insurance and access to health care services (Institute of Medicine 2009). The aims of this analysis are to use a national hospital discharge survey database to estimate the contribution of insurance status to access to health care resources and to neonatal survival outcome, adjusted for the diagnoses and demographic characteristics that are associated with neonatal death.

ObjectiveTo determine the effect of intention to breast-feed on short-term breast-feeding outcomes in women delivering term and preterm infants.DesignData from the US Centers for Disease Control and Prevention's Pregnancy Risk Assessment Monitoring System (PRAMS) for three states, Ohio, Michigan and Arkansas, during 2000–2003 were analysed. SAS 9·1·3 and SUDAAN 10 statistical software packages were used for analyses.SettingArkansas, Michigan and Ohio, USA.SubjectsMothers of recently delivered infants, selected by birth certificate sampling.ResultsOf 16 839 mothers included, 9·7 % delivered preterm. Some 52·2 % expressed definite intention to breast-feed, 16·8 % expressed tentative intention, 4·3 % were uncertain and 26·8 % had no intention to breast-feed. Overall 65·2 % initiated breast-feeding, 52·0 % breast-fed for ≥4 weeks and 30·8 % breast-fed for ≥10 weeks. Women with definite intention were more likely to initiate (OR = 24·3, 95 % CI 18·4, 32·1), to breast-feed for ≥4 weeks (OR = 7·12, 95 % CI 5·95, 8·51) and to breast-feed for ≥10 weeks (OR = 2·75, 95 % CI 2·20, 3·45) compared with women with tentative intention. Levels of intention did not differ between women delivering preterm and term. Women delivering at ConclusionsPrenatal intention to breast-feed is a powerful predictor of short-term breast-feeding outcomes in women delivering both at term and prematurely.

Background Red blood cell (RBC) transfusions in very low birthweight (VLBW) infants, while common, carry risk. Our objective was to determine clinical predictors of and trends in RBC transfusions among VLBW infants. Methods RBC transfusion practice and its clinical predictors in 1,750 VLBW (≤1500 g) infants were analyzed in a single-center cohort across sequential epochs: 2000–2004 (Epoch 1), 2005– 2009 (Epoch 2), and 2010–2013 (Epoch 3). Results Overall, 1,168 (67 %) infants received ≥1 transfusions. The adjusted likelihood of ≥1 transfusions decreased for each 1-g/dL increment in initial hemoglobin concentration following birth, for females, and for each 100-g increment in birthweight. The adjusted likelihood of ≥1 transfusions increased with infants receiving mechanical ventilation, with increasing length of hospital stay, with necrotizing enterocolitis and with non-lethal congenital anomalies requiring surgery. The adjusted mean (SEM) number of transfusions per patient was decreased in Epoch 3, compared with Epoch 1 and Epoch 2. For an initial hemoglobin of ≥16.5 g/dL, the predicted probability of being transfused was ≤50%. Conclusion Adjusted RBC transfusions declined and female sex conferred an unexplained protection over the study period. Modest increases in initial hemoglobin by placentofetal transfusion at delivery may reduce the need for RBC transfusion.

Importance Reduced death and neurodevelopmental impairment among infants is a goal of perinatal medicine. Objective To assess the association between surgery during the initial hospitalization and death or neurodevelopmental impairment of very low-birth-weight infants. Design, Setting, and Participants A retrospective cohort analysis was conducted of patients enrolled in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database from 1998 through 2009 and evaluated at 18 to 22 months’ corrected age. Twenty-two academic neonatal intensive care units participated. Inclusion criteria were birth weight 401 to 1500 g, survival to 12 hours, and availability for follow-up. A total of 12 111 infants were included in analyses. Exposures Surgical procedures; surgery also was classified by expected anesthesia type as major (general anesthesia) or minor (nongeneral anesthesia). Main Outcomes and Measures Multivariable logistic regression analyses planned a priori were performed for the primary outcome of death or neurodevelopmental impairment and for the secondary outcome of neurodevelopmental impairment among survivors. Multivariable linear regression analyses were performed as planned for the adjusted mean scores of the Mental Developmental Index and Psychomotor Developmental Index of the Bayley Scales of Infant Development, Second Edition, for patients born before 2006. Results A total of 2186 infants underwent major surgery, 784 had minor surgery, and 9141 infants did not undergo surgery. The risk-adjusted odds ratio of death or neurodevelopmental impairment for all surgery patients compared with those who had no surgery was 1.29 (95% CI, 1.08-1.55). For patients who had major surgery compared with those who had no surgery, the risk-adjusted odds ratio of death or neurodevelopmental impairment was 1.52 (95% CI, 1.24-1.87). Patients classified as having minor surgery had no increased adjusted risk. Among survivors who had major surgery compared with those who had no surgery, the adjusted risk of neurodevelopmental impairment was greater and the adjusted mean Bayley scores were lower. Conclusions and Relevance Major surgery in very low-birth-weight infants is independently associated with a greater than 50% increased risk of death or neurodevelopmental impairment and of neurodevelopmental impairment at 18 to 22 months’ corrected age. The role of general anesthesia is implicated but remains unproven.

To investigate whether observed vs expected (O/E) lung–to–head ratio (LHR) correlates with neonatal survival in infants with congenital diaphragmatic hernia (CDH). Secondary goal was to correlate O/E LHR with Oxygenation index (OI) in the first 12 hours of life.

Background To determine the effect of human milk, maternal and donor, on in-hospital growth of very low birthweight (VLBW) infants. We performed a retrospective cohort study comparing in-hospital growth in VLBW infants by proportion of human milk diet, including subgroup analysis by maternal or donor milk type. Primary outcome was change in weight z-score from birth to hospital discharge. Methods Retrospective cohort study. Results 171 infants with median gestational age 27 weeks (IQR 25.4, 28.9) and median birthweight 899 g (IQR 724, 1064) were included. 97% of infants received human milk, 51% received > 75% of all enteral intake as human milk. 16% of infants were small-for-gestational age (SGA, < 10th percentile) at birth, and 34% of infants were SGA at discharge. Infants fed >75% human milk had a greater negative change in weight z-score from birth to discharge compared to infants receiving < 75% (−0.6 vs, -0.4, p = 0.03). Protein and caloric supplementation beyond standard human milk fortifier was related to human milk intake (p = 0.04). Among infants receiving > 75% human milk, there was no significant difference in change in weight z-score by milk type (donor −0.84, maternal −0.56, mixed −0.45, p = 0.54). Infants receiving >75% donor milk had higher rates of SGA status at discharge than those fed maternal or mixed milk (56% vs. 35% (maternal), 21% (mixed), p = 0.08). Conclusions VLBW infants can grow appropriately when fed predominantly fortified human milk. However, VLBW infants fed >75% human milk are at greater risk of poor growth than those fed less human milk. This risk may be highest in those fed predominantly donor human milk.

OBJECTIVE: The goal was to examine the impact of birth at night, on the weekend, and during July or August (the first months of the academic year) and the impact of resident duty-hour restrictions on mortality and morbidity rates for very low birth weight infants. METHODS: Outcomes were analyzed for 11 137 infants with birth weights of 501 to 1250 g who were enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network registry in 2001–2005. Approximately one-half were born before the introduction of resident duty-hour restrictions in 2003. Follow-up assessments at 18 to 22 months were completed for 4508 infants. Mortality rate, short-term morbidities, and neurodevelopmental outcome were examined with respect to the timing of birth. RESULTS: There was no effect of the timing of birth on mortality rate and no impact on the risks of short-term morbidities except that the risk of retinopathy of prematurity (stage ≥2) was higher after the introduction of duty-hour restrictions and the risk of retinopathy of prematurity requiring operative treatment was lower for infants born during the late night than during the day. There was no impact of the timing of birth on neurodevelopmental outcome except that the risk of hearing impairment or death was slightly lower among infants born in July or August. CONCLUSION: In this network, the timing of birth had little effect on the risks of death and morbidity for very low birth weight infants, which suggests that staffing patterns were adequate to provide consistent care.

To determine genetic and clinical risk factors associated with elevated systolic blood pressure (ESBP) in preterm infants after discharge from the neonatal intensive care unit (NICU).A convenience cohort of infants born at32 weeks gestational age was followed after NICU discharge. We retrospectively identified a subgroup of subjects with ESBP (systolic blood pressure [SBP]90th percentile for term infants). Genetic testing identified alleles associated with ESBP. Multivariate logistic regression analysis was performed for the outcome ESBP, with clinical characteristics and genotype as independent variables.Predictors of ESBP were cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) (rs28360521) CC genotype (OR, 2.92; 95% CI, 1.48-5.79), adjusted for outpatient oxygen therapy (OR, 4.53; 95% CI, 2.23-8.81) and history of urinary tract infection (OR, 4.68; 95% CI, 1.47-14.86). Maximum SBP was modeled by multivariate linear regression analysis: maximum SBP=84.8 mm Hg + 6.8 mm Hg if cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) CC genotype + 6.8 mm Hg if discharged on supplemental oxygen + 4.4 mm Hg if received inpatient glucocorticoids (P=.0002).ESBP is common in preterm infants with residual lung disease after discharge from the NICU. This study defines clinical factors associated with ESBP, identifies a candidate gene for further testing, and supports the recommendation to monitor blood pressure before age 3 years, as is suggested for term infants.

A bar code medication administration (BCMA) system reduced preventable adverse drug events (ADEs) by 47% in our neonatal intensive care unit (NICU). However, it is often expected that providers will not welcome technological change. Two years after BCMA system implementation, we studied the perceptions of nurses in our NICU to better understand their opinions about patient safety, use, acceptance and occupational effects of the new technology. Forty-six nurses (median age < 30 years) completed a 30-item questionnaire. Most nurses reported comfort using the system within two weeks. The majority believed that the system had prevented a medication error or ADE, although they were aware that medication errors persisted and workarounds occurred. Most reported that medication administration required more time with the BCMA system, but they believed that the alerts, which most reported occurred with < or =25% scheduled administrations, were not excessive. Over half of the nurses felt that the new system improved job satisfaction and increased professionalism. Although overall stress levels were moderate, nurses reported greater stress resulting from computer breakdowns than from other situations. Nurses reported strong support from supervisors, physicians and hospital administrators. These nurses were adaptive to the new technology when they believed it increases patient safety, nursing professionalism and job satisfaction and when they were supported by colleagues.

Summary: Although glucose is an important fuel for fetal oxidative metabolism, regulation of its availability to the mammalian fetus is poorly understood. This study was performed to determine the effect of infusions of insulin into the uterine arterial circulation on umbilical uptake of glucose in chronically instrumented, unstressed sheep. Twenty-eight determinations of umbilical glucose uptake and diffusion clearance of glucose by the placenta were made in four ewes. Immediately following a control study during which saline was infused into the uterine artery, porcine regular insulin diluted in saline was infused at 0.05 to 8.1 mU/min · kg uterine weight for 20–30 min and the determinations were repeated. Subsequent studies were performed at the conclusion of additional infusions of insulin to a maximum of 21.6 mU/min · kg. There was a significant increase in umbilical glucose uptake during initial insulin infusions (4.47 ± 0.6 mg/min · kg fetus) compared to the control studies (3.08 ± 0.6 mg/min · kg) associated with an increase in diffusion clearance (13.8 ± 1.9 ml/min · kg fetus vs. 8.99 ±1.8 ml/min · kg). When the total cumulative dose of exogenous insulin, It, was 162 mU/kg uterine weight or less, the umbilical uptake of glucose, Q, may be expressed as a function of maternal arterial blood glucose concentration in milligrams per dl, [A], and of It. Speculation: Exogenous insulin infused at physiologic rates into the ovine uterine artery increases the permeability of the placenta to glucose by increasing the initial rate of glucose transport by a carrier system into cells which comprise the placenta until insulin receptor sites are saturated.

The activity of UDP-D-xylose: proteoglycan core protein β-D-xylosyltransferase (EC 2.4.2.26), the enzyme that catalyzes the initiation of the polysaccharide chain linkage to the core protein of proteoglycans, was measured in costal cartilage from 20 fetal sheep of 65-138 days gestation. Activity of the enzyme was estimated from the transfer of [14C]xylose from UDP-[14C]xylose to silk as the acceptor protein. The specific activity decreased approximately 10-fold and was found to be highly correlated with the decremental rate of growth in length of the fetal vertebral column. These observations, together with the known gestational decrease in the in vitro rate of uptake of radio labeled sulfate by ovine fetal cartilage, a subsequent step in proteoglycan synthesis, support the hypothesis that normal fetal skeletal growth is dependent during the last one-half of gestation on the activity of xylosyltransferase in cartilage.

Infusion of gastrin, G-17I, at 0.4 microgram/min into either the maternal or fetal venous circulation of six late gestation sheep was associated with increases in serum gastrin concentration in the infused circulation and reciprocal decreases in the serum gastrin concentration in the other circulation (contraplacental) that perfused the placenta. Pentagastrin infusion at 0.4 microgram/min was associated with an increase in C-terminal specific gastrin immunoreactivity in both the infused and the contraplacental circulations. These observations suggest that biologically active fragments of gastrin, but not the intact molecule, may cross the ovine placenta. An alternative explanation for our results is that gastrin infusion into either the maternal or fetal circulation which perfuses the placenta may result in the release of an inhibitor (i.e., somatostatin) into the other circulation. Of broad importance, these observations indicate that although intact polypeptide hormones may not traverse the placenta, their concentrations in maternal and fetal sera may not be as independent as previously believed. Serum gastrin half-life values in late gestation sheep fetuses, lambs, and ewes were determined to be 13.7 +/- 1.9, 16.7 +/- 2.6, and 15.2 +/- 2.8 min, respectively. These similar values indicate that the relatively high serum gastrin concentrations observed in near-term sheep fetuses are not the result of prolonged half-life in the fetus.

Summary: Human and ovine placental tissue homogenates were assayed for dipeptidase activity in vitro. Glycyl-L-leucine, L-leucyl glycine, glycyl-L-lysine, and L-lysyl glycine were hydrolyzed by placental homogenates. The pH optimum for the reaction was 8.0. The relationship between enzyme activity and concentration was linear for placental homogenate concentrations between 0.01 and 0.10 mg protein/ml of reaction mixture. Enzyme activities were 1.92 ± 0.12 (S.E.) μoles/min/mg protein for hydrolysis of glycyl-L-leucine, 0.34 ± 0.06 (S.E.) μmoles/min/mg protein, for hydrolysis of glycy-L-lysine by human placenta, and 2.79 ± 0.8U μmoles/min/mg protein and 0.41 ± 0.25 μmoles/min/mg protein, respectively, by ovine placenta. The infusion of glycyl-L-lucine into the uterine artery of unstressed catheterized pregnant ewes yielded increased concentrations of both component amino acids in uterine venous blood and of leucine in umbilical venous blood. Speculation: The presence of dipeptidase activity in placental homogenates and the observation that glycyl-L-leucine when infused into the main uterine artery is hydrolyzed to its component amino acids support the hypothesis that leucine and possibly glycine extracted from the placenta by the umbilical circulation may be provided by placental hydrolysis of dipeptides which arise within the placenta from the degradation of larger peptides and proteins.

Summary: The purpose of the present study was to investigate the postnatal development of lower esophageal spincter (LES) competence in the beagle and to determine the role of gastrin in LES functional ontogeny. Eleven beagle puppies taken from two litters were studied. All puppies were allowed to suckle during the first 3 postnatal wk. In the 4th wk, all puppies were weaned, and by the 5th wk only solid chow was offered. Intraluminal manometric pressure determinations were obtained in unanesthetized, unsedated puppies using twin-lumen, 1.7 mm OD, 1 mm ID polyvinyl catheters. A 12–15 min baseline period of intraluminal pressure was monitored, after which the puppies received successive doses of 0.03, 0.1, 1.0, and 8.0 μg/kg pentagastrin (PG) SC spaced at 45-min intervals. Progressive increases in LES pressure both during basal periods and during gastric contractions and in gastric fundus (GF) pressures during gastric contractions occurred during the 1st 5 weeks of life. An increase in pressure gradient between the LES and GF during gastric contraction occurred from birth through 5 wk of age. There was no response to 0.1–8.0 μg/kg PG until postnatal days 5–6 when the LES pressure gradient in the basal state increased in response to each of these doses. There was also no significant response by the LES to PG during gastric contraction until days 11–12 when all doses of PG evoked enhancement of LES pressure. These studies suggest that an increase in LES-GF intraluminal pressure gradient develops during the initial 2 postnatal wk in this species and that this development does not involve the hormone gastrin. Later, however, the pressure gradient may depend upon both age and gastrin since a two-way analysis of variance indicated that not only is LES pressure affected by postnatal age and by PG dose, but that there is an interaction between postnatal age and PG dose which is significant. By the fifth wk, there was an apparent dose-response effect in which the lower two doses produced increased LES pressure and the larger two doses produced decreased LES pressures. Speculation: Gastroesophageal reflux (GER) in some infants may occur when the developmental interplay between endogenous gastrin concentration, increasing sensitivity to gastrin by LES, and sensitivity to gastrin by the muscular stomach proceeds abnormally. Alternatively, either the postnatal increase in LES muscle mass or the maturation of a neural pathway that mediates reflex contraction of the LES during gastric contraction, or both, may be delayed or abnormal in some children with GER. A fourth possible abnormality that may permit GER in still other infants is failure to generate the increasing gastric contraction rate and intraluminal pressures observed to occur in normal development, thus permitting delayed gastric emptying.

Extract: Glucose/oxygen quotients were determined across the hindlimbs of seven fetuses, for a total of five studies in fetuses of fed ewes and five studies in fetuses of fasted ewes. The glucose/oxygen quotient was found to be a function of the fetal arterial glucose concentration in mM, [a], described by the equation: glucose/oxygen quotient = - 0.047 + 1.46[a]. The dependence of glucose uptake by the fetal hindlimb upon arterial glucose concentration is the first demonstration of the effect of substrate availability on the metabolism of a fetal organ. Speculation: The demonstration of glucose/oxygen quotients of 1.0 or greater for fetal tissues at a time in gestation when the umbilical glucose/oxygen quotient is 0.4–0.5 suggests two possible explanations: (1) there may be substrate specificity for oxidative metabolism for each fetal organ, and (2) non-glucose substrates such as amino acids taken up by the umbilical circulation may be utilized by the fetal liver for gluconeogenesis.

To determine the relationship between fetal and maternal plasma insulin concentrations (If, Im) and umbilical uptake of glucose (Qg) and lactate (Ql) in sheep, 6 ewes of 120-130 days gestation were prepared with indwelling catheters in the umbilical vein, fetal pedal artery and vein, and maternal uterine and femoral arteries. Fed state Qg, Ql, If, and I were determined at intervals from the 2nd to the 11th postoperative day (POD). Qg and Ql were determined by the Fick principle employing steady state diffusion of antipyrine to determine umbilical blood flow. Studies were performed before (control n=15) and after (n=15) the perfusion of the uterine artery with ovine insulin 7.5 mU/kg ewe/30 min. Insulin was measured by radioimmunoassay. Results: Control If and Im in μ U/ml increased with increasing POD as described by the following regression equations: If = 0.76 POD + 3.74, (F ratio, p < .025), and Im = 1.86 POD + 8.61, (p < .05). Uterine artery insulin infusion increased Im but did not affect If or Ql. The postoperative increase in If from 5.5-16.0μ μ U/ml was associated with a decrease in Ql in mM/min/kg fetus: Ql = -0.004 If + 0.072 (p < .025). Qg was unrelated to POD, Ql, or If. Conclusions: These studies (1) confirm the lack of ovine insulin transfer across the ovine placenta in vivo, (2) demonstrate increasing Im and If for as long as 11 days after surgery and resumption of maternal nutrition, and (3) show that umbilical lactate uptake is inversely related to fetal plasma insulin concentration, but is independent of umbilical glucose uptake and of maternal plasma insulin concentration.

Recent studies of fetal sheep metabolism in unstressed preparations have suggested that amino acids (AA) may furnish up to 25% of the substrate for fetal aerobic metabolism after 125 days gestational age (GA). This investigation was performed to determine throughout gestation the activities in fetal sheep liver and kidney of key enzymes for gluconeogenesis. Tissue specimens from 10 fetuses of well-nourished ewes at 44-145 d. GA were assayed by spectrophotometric methods. Results: (1) After 125 d. GA substantial activities were found in both liver and kidney for glucose-6-p'tase (G6P), fructose-1,6-dipTtase (F1,6DP), pyruvate carboxylase, PEP carboxykinase, aspartate aminotransferase (asp AT), and alanine aminotransferase (ala AT). The activity in kidney for each enzyme except asp AT was comparable to or greater than the activity in liver.(2) Activities of 2 enzymes increased with gestation: Conclusion: Significant activities of these enzymes in late gestation support the theories of fetal utilization of AA (a) as substrate for aerobic metabolism, and (b) for gluconeogenesis. Speculations: (1) Increasing capability for gluconeogenesis may occur as gestation proceeds. (2) The role of the kidney in overall fetal metabolism may be substantial. (* μM Pi produced/min/g. protein; x ± SEM)

The postnatal development of gastric motility and pH, and the response to pentagastrin (PG) were studied at 10 intervals in 5 beagles from birth to 6 weeks. Motility was monitored using twin single lumen 1.7 mm catheters with 1 mm side openings at the tips which were 2 cm apart. Catheters were perfused with distilled H2O at a constant rate and pressure transducers were interposed in the system. Oral catheter insertion distance to the antrum of the stomach was determined radiographically. Puppies were fasted 3-6 hours prior to study; gastric contents were aspirated, and the stomach rinsed with distilled H2O. After an initial gastric pH determination and a 10-20 min. period of baseline motility monitoring, the response to 8 μ g/kg of s.c. PG was determined. Baseline mean antral contractions increased from 0.25/min on day 1 to 2.0/min on day 1 through weaning in the 4th week when the frequency decreased to 6.0 until day 7 when mean pH was 3.4. PG produced a significant decrease in pH on day 3 (p < 0.05), but the maximum decrease did not appear until day 9 and thereafter (p < 0.005). PG inhibition of the frequency and force of antral contractions was apparent from the 3rd day through the 6th week. These observations in beagle puppies suggest a developmental maturation in gastric motility and acid secretion from birth through the 2nd week, and a delay in responsiveness to PG.

We studied the maturation of the lower esophageal sphincter (LES) function in 17 infants without apnea at 29-41 wk postconceptual age (PCA) using an indwelling manometry system with a response rate of 90 mm Hg/sec. LES pressure was measured as the mean of peak pressures obtained during replicate pull-through maneuvers with a 3-lumen catheter. Initial studies obtained in each infant revealed no change in LES pressure with advancing fetal age. Subsequent studies revealed no change during 3 postnatal wks in LES pressure from the first wk pressure of 55.5 ± 4 (x + SE) mm Hg. However, LES pressure decreased in the 4th postnaTal wk corresponding with 36 wk PCA. We studied 26 additional infants of similar PCA who had apnea that was treated beginning at 7.7 ± 1.1 d with theophylline (THEO). The mean LES pressure in these infants was 69.2 ± 9.4 mm Hg before therapy and 75 ± 5.6 mm Hg during therapy, both greater values than that of infants without apnea (p < 0.0002). LES pressure did not decrease in apneic infants on THEO, but remained elevated for 7 postnatal wks. Conclusions: (1) LES pressures are greater in preterm infants than in older infants; (2) beginning at 36 wks PCA, LES pressures decrease in normal infants; (3) preterm infants with apnea have greater LES pressures before and during THEO therapy than preterm babies without apnea, suggesting an associated pathophysiologic mechanism that is not interrupted by THEO.

To test whether insufficient calcium (Ca), phosphorus (P) or vitamin D (D) to support mineralization was delivered to rapidly growing VLBW ( R (p R but R; none developed rickets. ΔD/ΔWt was ≥CON in 11/11. Growth rates did not differ from R or CON. These data suggest that ≥3.82 mg Ca/g wt gain and ≥1.73 mg P/g wt gain, when provided primarily IV with adequate D, are sufficient to prevent rickets in growing VLBW infants. In 3 R patients under treatment, healing was diagnosed when mineral intakes reached or exceeded these values.

Top of pageAbstract To test the hypothesis that fetal skeletal growth decreases in late gestation because the reported decline in serum sulfate conc ([SO4]) limits SO4 for incorporation into glycosaminoglycans by cartilage, 6 fetal sheep were perfused with Na2SO4 2.2 g/h i.v. for 7 d. As controls, the twin of each fetus was perfused with equimolar NaCl. Costal cartilage was harvested at GA=134 d and assayed in vitro for 35SO4 uptake (QSO4, μ g/24h/mg cartilage adjusted per mg SO4/tube) in the presence of 0, 10% and 20% normal human serum (NHS). Sera sampled before and during perfusion were assayed for [SO4]. Pairwise comparison of twin fetuses reveals SO4-perfusion produces a 34-47% increase in QSO4 independent of [NHS], compared to the ~300% increase in QSO4 produced by 20% NHS. Fetal wt, length, and sex were not different between groups. These results demonstrate that although late fetal cartilage in vitro QSO4 may be increased by elevating the fetal serum [SO4], other serum factors are more important determinants of fetal cartilage metabolic activity. The decrease in [SO4] observed from mid-gestation to term likely represents depletion of the SO4 pool by fetal growth processes rather than a decreased availability of SO4 that restricts growth.

To investigate the neonatal development of upper small bowel (SB) peristalsis and the effect of pentagastrin (PG) on motility, we monitored duodenal intraluminal pressure manometrically in 11 beagle puppies from birth until weaning at 5 wk. The response rate of the system employed was 150 mm Hg/sec. Electrodes were implanted on the SB serosal surface for subsequent monitoring of myoelectric activity during the first 2 mo. in 3 add'l puppies. During the first 3 wk there was an increase in duodenal contraction rate immediately after a liquid meal from 11±0.4/min to 16±1/min (p

To determine the effect of decreasing systemic oxygen delivery (SOD) on oxygen consumption (Vo2) in the growing neonatal subject, we conducted 15 studies in 5 three week old lambs. SOD was lowered by progressive pericardial tamponade. SOD was measured as the product of cardiac output (CO) and arterial oxygen content. CO was measured by thermodilution. Pulmonary mixed venous and arterial blood were used to measure Po2, O2 saturation and hgb. Measurements were made every twenty minutes in unanesthetized, spontaneously breathing lambs in which decremental decreases in CO were produced. The change in Vo2 with decreasing SOD was analyzed by grouping data in decreasing ranges of SOD. The chart presents the mean± SD in each range