Association of haemoglobin levels in the first trimester and at 26-30 weeks with fetal and neonatal outcomes: a secondary analysis of the Global Network for Women's and Children's Health's ASPIRIN Trial.

OBJECTIVE: Limited data are available from low- and middle-income countries (LMICs) on the relationship of haemoglobin levels to adverse outcomes at different times during pregnancy. We evaluated the association of haemoglobin levels in nulliparous women at two times in pregnancy with pregnancy outcomes. DESIGN: ASPIRIN Trial data were used to study the association between haemoglobin levels measured at 6+0 -13+6  weeks and 26+0 -30+0  weeks of gestation with fetal and neonatal outcomes. SETTING: Obstetric care facilities in Pakistan, India, Kenya, Zambia, The Democratic Republic of the Congo and Guatemala. POPULATION: A total of 11 976 pregnant women. METHODS: Generalised linear models were used to obtain adjusted relative risks and 95% CI for adverse outcomes. MAIN OUTCOME MEASURES: Preterm birth, stillbirth, neonatal death, small for gestational age (SGA) and birthweight <2500 g. RESULTS: The mean haemoglobin levels at 6+0 -13+6  weeks and at 26-30 weeks of gestation were 116 g/l (SD 17) and 107 g/l (SD 15), respectively. In general, pregnancy outcomes were better with increasing haemoglobin. At 6+0 -13+6  weeks of gestation, stillbirth, SGA and birthweight <2500 g, were significantly associated with haemoglobin of 70-89 g/l compared with haemoglobin of 110-129 g/l The relationships of adverse pregnancy outcomes with various haemoglobin levels were more marked at 26-30 weeks of gestation. CONCLUSIONS: Both lower and some higher haemoglobin concentrations are associated with adverse fetal and neonatal outcomes at 6+0 -13+6  weeks and at 26-30 weeks of gestation, although the relationship with low haemoglobin levels appears more consistent and generally stronger. TWEETABLE ABSTRACT: Both lower and some higher haemoglobin concentrations were associated with adverse fetal and neonatal outcomes at 6-13 weeks and 26-30 weeks of gestation.

Cost estimation alongside a multi-regional, multi-country randomized trial of antenatal ultrasound in five low-and-middle-income countries.

BACKGROUND: Improving maternal health has been a primary goal of international health agencies for many years, with the aim of reducing maternal and child deaths and improving access to antenatal care (ANC) services, particularly in low-and-middle-income countries (LMICs). Health interventions with these aims have received more attention from a clinical effectiveness perspective than for cost impact and economic efficiency. METHODS: We collected data on resource use and costs as part of a large, multi-country study assessing the use of routine antenatal screening ultrasound (US) with the aim of considering the implications for economic efficiency. We assessed typical antenatal outpatient and hospital-based (facility) care for pregnant women, in general, with selective complication-related data collection in women participating in a large maternal health registry and clinical trial in five LMICs. We estimated average costs from a facility/health system perspective for outpatient and inpatient services. We converted all country-level currency cost estimates to 2015 United States dollars (USD). We compared average costs across countries for ANC visits, deliveries, higher-risk pregnancies, and complications, and conducted sensitivity analyses. RESULTS: Our study included sites in five countries representing different regions. Overall, the relative cost of individual ANC and delivery-related healthcare use was consistent among countries, generally corresponding to country-specific income levels. ANC outpatient visit cost estimates per patient among countries ranged from 15 to 30 USD, based on average counts for visits with and without US. Estimates for antenatal screening US visits were more costly than non-US visits. Costs associated with higher-risk pregnancies were influenced by rates of hospital delivery by cesarean section (mean per person delivery cost estimate range: 25-65 USD). CONCLUSIONS: Despite substantial differences among countries in infrastructures and health system capacity, there were similarities in resource allocation, delivery location, and country-level challenges. Overall, there was no clear suggestion that adding antenatal screening US would result in either major cost savings or major cost increases. However, antenatal screening US would have higher training and maintenance costs. Given the lack of clinical effectiveness evidence and greater resource constraints of LMICs, it is unlikely that introducing antenatal screening US would be economically efficient in these settings--on the demand side (i.e., patients) or supply side (i.e., healthcare providers). TRIAL REGISTRATION: Trial number: NCT01990625 (First posted: November 21, 2013 on https://clinicaltrials.gov ).

Global Network for Women's and Children's Health Research: probable causes of stillbirth in low- and middle-income countries using a prospectively defined classification system.

OBJECTIVE: We sought to classify causes of stillbirth for six low-middle-income countries using a prospectively defined algorithm. DESIGN: Prospective, observational study. SETTING: Communities in India, Pakistan, Guatemala, Democratic Republic of Congo, Zambia and Kenya. POPULATION: Pregnant women residing in defined study regions. METHODS: Basic data regarding conditions present during pregnancy and delivery were collected. Using these data, a computer-based hierarchal algorithm assigned cause of stillbirth. Causes included birth trauma, congenital anomaly, infection, asphyxia, and preterm birth, based on existing cause of death classifications and included contributing maternal conditions. MAIN OUTCOME MEASURES: Primary cause of stillbirth. RESULTS: Of 109 911 women who were enrolled and delivered (99% of those screened in pregnancy), 2847 had a stillbirth (a rate of 27.2 per 1000 births). Asphyxia was the cause of 46.6% of the stillbirths, followed by infection (20.8%), congenital anomalies (8.4%) and prematurity (6.6%). Among those caused by asphyxia, 38% had prolonged or obstructed labour, 19% antepartum haemorrhage and 18% pre-eclampsia/eclampsia. About two-thirds (67.4%) of the stillbirths did not have signs of maceration. CONCLUSIONS: Our algorithm determined cause of stillbirth from basic data obtained from lay-health providers. The major cause of stillbirth was fetal asphyxia associated with prolonged or obstructed labour, pre-eclampsia and antepartum haemorrhage. In the African sites, infection also was an important contributor to stillbirth. Using this algorithm, we documented cause of stillbirth and its trends to inform public health programs, using consistency, transparency, and comparability across time or regions with minimal burden on the healthcare system. TWEETABLE ABSTRACT: Major causes of stillbirth are asphyxia, pre-eclampsia and haemorrhage. Infections are important in Africa.

A prospective cause of death classification system for maternal deaths in low and middle-income countries: results from the Global Network Maternal Newborn Health Registry.

OBJECTIVE: To describe the causes of maternal death in a population-based cohort in six low- and middle-income countries using a standardised, hierarchical, algorithmic cause of death (COD) methodology. DESIGN: A population-based, prospective observational study. SETTING: Seven sites in six low- to middle-income countries including the Democratic Republic of the Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. POPULATION: All deaths among pregnant women resident in the study sites from 2014 to December 2016. METHODS: For women who died, we used a standardised questionnaire to collect clinical data regarding maternal conditions present during pregnancy and delivery. These data were analysed using a computer-based algorithm to assign cause of maternal death based on the International Classification of Disease-Maternal Mortality system (trauma, termination of pregnancy-related, eclampsia, haemorrhage, pregnancy-related infection and medical conditions). We also compared the COD results to healthcare-provider-assigned maternal COD. MAIN OUTCOME MEASURES: Assigned causes of maternal mortality. RESULTS: Among 158 205 women, there were 221 maternal deaths. The most common algorithm-assigned maternal COD were obstetric haemorrhage (38.6%), pregnancy-related infection (26.4%) and pre-eclampsia/eclampsia (18.2%). Agreement between algorithm-assigned COD and COD assigned by healthcare providers ranged from 75% for haemorrhage to 25% for medical causes coincident to pregnancy. CONCLUSIONS: The major maternal COD in the Global Network sites were haemorrhage, pregnancy-related infection and pre-eclampsia/eclampsia. This system could allow public health programmes in low- and middle-income countries to generate transparent and comparable data for maternal COD across time or regions. TWEETABLE ABSTRACT: An algorithmic system for determining maternal cause of death in low-resource settings is described.

Routine antenatal ultrasound in low- and middle-income countries: first look - a cluster randomised trial.

OBJECTIVE: Ultrasound is widely regarded as an important adjunct to antenatal care (ANC) to guide practice and reduce perinatal mortality. We assessed the impact of ANC ultrasound use at health centres in resource-limited countries. DESIGN: Cluster randomised trial. SETTING: Clusters within five countries (Democratic Republic of Congo, Guatemala, Kenya, Pakistan, and Zambia) METHODS: Clusters were randomised to standard ANC or standard care plus two ultrasounds and referral for complications. The study trained providers in intervention clusters to perform basic obstetric ultrasounds. MAIN OUTCOME MEASURES: The primary outcome was a composite of maternal mortality, maternal near-miss mortality, stillbirth, and neonatal mortality. RESULTS: During the 24-month trial, 28 intervention and 28 control clusters had 24 263 and 23 160 births, respectively; 78% in the intervention clusters received at least one study ultrasound; 60% received two. The prevalence of conditions noted including twins, placenta previa, and abnormal lie was within expected ranges. 9% were referred for an ultrasound-diagnosed condition, and 71% attended the referral. The ANC (RR 1.0 95% CI 1.00, 1.01) and hospital delivery rates for complicated pregnancies (RR 1.03 95% CI 0.89, 1.20) did not differ between intervention and control clusters nor did the composite outcome (RR 1.09 95% CI 0.97, 1.23) or its individual components. CONCLUSIONS: Despite availability of ultrasound at ANC in the intervention clusters, neither ANC nor hospital delivery for complicated pregnancies increased. The composite outcome and the individual components were not reduced. TWEETABLE ABSTRACT: Antenatal care ultrasound did not improve a composite outcome that included maternal, fetal, and neonatal mortality.

Intravenous glucose suppresses glucose production but not proteolysis in extremely premature newborns.

To ascertain whether the inability to suppress glucose production and increase glucose utilization in response to glucose infusion is an inherent characteristic of immature individuals, we determined glucose rate of appearance (R(a)) in minimally stressed, clinically stable, extremely premature infants (approximately 26-wk gestation) at two glucose infusion rates (6.2 +/- 0.4 and 9.5 +/- 0.5 mg/kg per min). We also assessed whether an increase in glucose delivery suppresses proteolysis by measuring the R(a) of phenylalanine and leucine. Glucose R(a) (and utilization) increased significantly at the higher glucose infusion rate (7.9 +/- 0.5 vs. 9.8 +/- 0.6 mg/kg per min). Glucose production persisted at the lower glucose infusion rate but was suppressed to nearly zero at the higher rate (1.7 +/- 0.5 vs. 0.3 +/- 0.1 mg/kg per min). Proteolysis was unaffected by the higher glucose infusion rate as reflected by no change in the rates of appearance of either phenylalanine (96 +/- 5 vs. 95 +/- 3 mumol/kg per h) or leucine (285 +/- 20 vs. 283 +/- 14 mumol/kg per h). Thus, clinically stable, extremely premature infants suppress glucose production and increase glucose utilization in response to increased glucose infusion, demonstrating no inherent immaturity of these processes. In contrast, increasing the rate of glucose delivery results in no change in whole body proteolysis in these infants. The regulation of proteolysis in this population remains to be defined.

Proteolysis and phenylalanine hydroxylation in response to parenteral nutrition in extremely premature and normal newborns.

To determine to what extent intravenous nutrition can reduce proteolysis in very immature and normal newborns, and to assess the capacity of preterm and normal newborns to convert phenylalanine to tyrosine, phenylalanine and leucine kinetics were measured under basal conditions and during parenteral nutrition in clinically stable, extremely premature (approximately 26 wk of gestation) infants and in normal term newborns. In response to parenteral nutrition, there was significantly less suppression (P < 0.001) of endogenous leucine and phenylalanine rate of appearance in extremely premature infants compared with term infants. Phenylalanine utilization for protein synthesis during parenteral nutrition increased significantly (P < 0.01) and by the same magnitude (approximately 15%) in both extremely premature and term infants. Phenylalanine was converted to tyrosine at substantial rates in both extremely premature and term infants; however, this conversion rate was significantly higher (P < 0.05) in extremely premature infants during both the basal and parenteral nutrition periods. These data provide clear evidence that there is no immaturity in the phenylalanine hydroxylation pathway. Furthermore, although parenteral nutrition appears to produce similar increases in protein synthesis in extremely premature and term infants, proteolysis is suppressed much less in extremely premature newborns. The factors responsible for this apparent resistance to suppression of proteolysis in the very immature newborn remain to be elucidated.

Skeletal muscle proteolysis is reduced in noninsulin-dependent diabetes mellitus and is unaltered by euglycemic hyperinsulinemia or intensive insulin therapy.

To assess how noninsulin-dependent diabetes mellitus (NIDDM) and diabetes control may alter whole body and skeletal muscle proteolysis, we measured the rate of appearance (Ra) of phenylalanine (reflecting proteolysis) in the whole body and across the leg (reflecting skeletal muscle), using a constant tracer infusion of [2H5]phenylalanine in the basal state and during high-dose euglycemic hyperinsulinemia in 6 NIDDM and 10 control subjects. Studies were performed in NIDDM subjects 2 weeks after complete withdrawal of antidiabetic treatment and again after intensive insulin therapy. After intensive treatment, significant reductions were measured in hemoglobin A1C, fasting glucose concentrations, and basal hepatic glucose output. In contrast, there was no change after therapy in basal whole body or leg phenylalanine Ra. Compared with that of controls, whole body phenylalanine Ra was significantly higher and leg phenylalanine Ra significantly lower in NIDDM subjects. During euglycemic hyperinsulinemia, whole body phenylalanine Ra was significantly suppressed (approximately 15%) below basal values before and after therapy in NIDDM subjects and similarly suppressed in control subjects. However, in NIDDM subjects, euglycemic hyperinsulinemia did not reduce leg phenylalanine Ra below basal values either before or after therapy, whereas hyperinsulinemia resulted in a 42% suppression of leg phenylalanine Ra in controls. We conclude that 1) the clear improvement in glucose metabolism produced by intensive insulin therapy in NIDDM is not accompanied by changes in whole body or skeletal muscle proteolysis; 2) skeletal muscle proteolysis is reduced even though whole body proteolysis is increased in NIDDM subjects compared with controls; and 3) although a high-dose systemic infusion of insulin significantly reduces whole body proteolysis in both NIDDM and control subjects, skeletal muscle proteolysis is suppressed only in controls. We speculate that in NIDDM, high basal insulin concentrations (approximately 200 pmol/L, unaltered by therapy) maximally suppress skeletal muscle proteolysis, and therefore higher insulin concentrations produce no additional suppression in skeletal muscle.

Leucine kinetics after a brief fast and in response to feeding in premature infants.

To examine how feeding affects changes in leucine and protein metabolism, leucine kinetics were determined in nine preterm infants (32 +/- 2 wk gestation; mean +/- SD) after a brief fast and again during hourly feedings. Rates of leucine oxidation were similar during the fasting and feeding periods (31 +/- 4 vs 37 +/- 6 mumol.kg-1.h-1; mean +/- SE). The nonoxidative disposal rates of leucine (a reflection of protein synthesis) were also similar during both periods (228 +/- 20 vs 205 +/- 10 mumol.kg-1.h-1; mean +/- SE). In contrast, the rates of leucine release from endogenous protein (an indication of protein breakdown) were significantly reduced by feeding (259 +/- 23 vs 185 +/- 11 mumol.kg-1.h-1; mean +/- SE, P = 0.02). A significant positive correlation was demonstrated between the fasting rate of leucine release from endogenous protein and the degree of suppression produced by feeding (r2 = 0.796, P = 0.001). Conversely, a significant inverse correlation was shown between the nonoxidative disposal rate of leucine during fasting and the increase in response to feeding (r2 = 0.848, P < 0.001). These data suggest that premature infants respond to feeding after a brief fast by suppressing protein breakdown, rather than by increasing protein synthesis, and changes in protein metabolism produced by feeding in premature newborns may be influenced by the prevailing rates of protein breakdown and synthesis during fasting.

Dietary carbohydrate assimilation in the premature infant: evidence for a nutritionally significant bacterial ecosystem in the colon.

Carbohydrate energy absorption and breath hydrogen concentration were measured in 12 premature infants 28-32 wk gestational age and 2-4 wk postnatal age. Each of two groups of six infants were randomly assigned to receive one of two formulas that differed only in carbohydrate source: 100% lactose (LAC) or 50% lactose: 50% glucose polymer (LAC + GP). In 11 infants the peak breath hydrogen concentration suggested extensive colonic fermentation (range 44-239 ppm/5% CO2 or 44-239 microL/L per 50 mL/L CO2). An approximate 100% increase in lactose intake in the LAC group was associated with a similar increase in breath hydrogen concentration at 30, 60, and 120 min. None of the infants exhibited diarrhea or vomiting or developed delayed gastric emptying. Carbohydrate energy absorption (mean +/- SD) was, respectively, 86 +/- 5% and 91 +/- 3% in the LAC and the LAC + GP groups (p greater than 0.05). Thus, colonic bacterial fermentation may be critical to energy balance and to the prevention of osmotic diarrhea in premature infants fed lactose.

Reduction of neonatal mortality after multiple doses of bovine surfactant in low birth weight neonates with respiratory distress syndrome.

To determine if outcomes of low birth weight neonates with respiratory distress syndrome can be improved by the administration of multiple doses of bovine surfactant, we conducted two identical multicenter, controlled trials, and the results were combined for analysis. Seven hundred and ninety-eight neonates weighing 600 to 1750 g at birth who had developed respiratory distress syndrome within 6 hours of birth were assigned randomly to receive either 100 mg of phospholipid/kg of Survanta, a modified bovine surfactant (n = 402), or a sham dosing procedure (n = 396). Neonates whose respiratory distress persisted could be given up to three more doses, with all doses to be given in the first 48 hours after birth. Dosing was performed by investigators not involved in the clinical care of the neonates; nursery staff were kept blinded as to the treatment assignment. Fewer Survanta-treated neonates died of any cause (18.4% vs 27.3%, P = .002), died of respiratory distress syndrome (9.0% vs 20.3%, P less than .001), and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome (51.2% vs 64.6%, P less than .001). Neonates who received Survanta also had greater improvement in their oxygenation and ventilatory status from baseline to 72 hours than did control neonates. Survanta-treated neonates were at lowered risk for developing pulmonary interstitial emphysema (18.6% vs 39.3%, P less than .001) and other pulmonary air leaks (11.5% vs 25.9%, P less than .001). We conclude that multiple doses of Survanta given after diagnosis of respiratory distress syndrome reduce mortality and morbidity.

Effects of intravenous insulin-like growth factor-I and insulin administration on insulin-like growth factor-binding proteins in the ovine fetus.

The insulin-like growth factors (IGF) are important anabolic hormones in the mammalian fetus; their anabolic actions are potentially modulated by alterations in the IGF-binding proteins (IGFBP). We have previously shown that the nutritional state of the fetus affects both IGF-I and the IGFBP concentrations. The present study was designed to determine the effect of alterations in insulin and IGF-I circulating concentrations on the IGFBPs. Because both insulin and IGF-I elicit decreases in glucose and amino acid concentrations, the concentrations of these substrates were clamped during the hormone infusions. Sixteen ovine fetuses were chronically catheterized at approximately 115 days of gestation, and experimental procedures performed at approximately 130 days of gestation. Insulin, IGF-I or both were infused for an 8-h period. Baseline concentrations of hormones and binding proteins were obtained, and concentrations were also obtained at the end of the infusion. Hepatic IGFBP-1 mRNA expression was also determined. Intravenous infusion of IGF-I significantly increased IGF-I concentrations in plasma in the ovine fetus. Intravenous infusion of insulin inhibited hepatic IGFBP-1 gene expression when amino acids and glucose were clamped. In contrast, intravenous infusion of recombinant human IGF-I (rhIGF-I) enhanced hepatic IGFBP-1 gene expression. Neither insulin nor rhIGF-I treatment had an effect on hepatic IGFBP-3 gene expression. Insulin did not alter plasma IGFBP-1 significantly, but it increased IGFBP-3 in plasma. rhIGF-I increased both IGFBP-1 and IGFBP-3 protein levels in plasma. The responses of IGFBP-1 and IGFBP-3 to increased plasma IGF-I and insulin may serve to protect the fetus from exaggerated anabolic effects and to blunt the hypoglycemic potential of circulating IGFs and insulin.

Effectiveness of two feeding methods in improving energy intake and growth of infants with cleft palate: a randomized study.

OBJECTIVE: To compare two feeding methods advocated for infants with cleft palate: (a) a squeezable plastic container with a narrow, long crosscut nipple (squeezable cleft palate nurser); and (b) a standard nipple with a crosscut (crosscut nipple). The effectiveness of a nutrition intervention protocol for these infants was also documented. DESIGN: Thirty-one infants (median age = 15 days) were randomized to one of two feeding methods (18 infants, squeezable cleft lip/palate nurser; 13 infants, crosscut nipple) within sex (21 boys, 10 girls) and palatal defect (22 cleft lip and palate, 9 isolated cleft palate) categories. The intervention included feeding technique instructions, nutrition counseling at each clinic visit, use of the same 20 kcal/oz standard formula for 12 months, and introduction of infant and soft table foods at 6 months. Four-day food records and growth data were obtained. MAIN OUTCOME MEASURES: Mean energy and protein intakes at 3 and 6 months of age and growth measurements during the first 18 months of life were obtained. STATISTICAL ANALYSES: A repeated measures analysis of variance for intakes was performed with time as the repeated measure and feeding method as the covariable. Similar analyses were completed for growth measures with sex and feeding method as covariates. RESULTS: Mean energy intake at 3 and 6 months of age (P = .24) and growth measurements during the first 18 months of life (P values: weight gain [grams per day], .73; weight, .21; length, .07; head circumference, .18; triceps and subscapular skinfolds and mid-arm circumference, .47, .48, and .69, respectively) were not significantly different. Both feeding methods were effective in supporting normal growth. APPLICATIONS: With adequate instruction related to the use of either feeding technique and close nutrition follow-up early in infancy, a dietitian or other health care practitioner may advise the use of either feeding method. These data support the need for feeding and nutrition education and early nutrition intervention.

Blood ammonia concentration in cord blood during pregnancy.

UNLABELLED: In vivo studies in several animal species and in vitro studies of human placenta suggest that ammonia is produced within the uteroplacenta and released into the fetal and maternal circulations. Furthermore, the fetal blood ammonia levels in sheep have been found to be significantly greater than maternal levels and inversely correlated with gestational age. Our present study had two main goals: first, to assess whether ammonia may be produced in the human placenta and taken up by the fetus and second, to determine if the fetal blood ammonia levels are greater than maternal and inversely correlated to gestational age. We measured the blood concentrations of ammonia by obtaining both umbilical venous (UV) and arterial (UA) samples obtained from doubly clamped sections of umbilical cord at the time of delivery. Blood gases and glucose were also measured on each sample. Samples were obtained at 96 deliveries (70 vaginal, 26 cesarean section, 18/26 cesarean deliveries not in labor). The deliveries were separated into two groups. Group A included all deliveries, both vaginal and cesarean section, while Group B consisted of only cesarean section prior to onset of labor. The mean gestational age for all deliveries was 38.4 weeks +/- 2.95 (S.D.) with a range of 25-43 weeks of gestation. There was no significant relationship between the fetal ammonia levels and gestational age in either group. In both groups A and B, the UA ammonia concentrations were significantly higher than the paired UV ammonia levels (UV-UA: Group A: -10.00 +/- 17.6, Group B: -9.3 +/- 12.6). CONCLUSION: These data show no correlation between fetal ammonia levels and gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Sepsis in asymptomatic term newborns delivered of antibiotic-treated mothers.

This study was undertaken to assess the incidence of culture-proved sepsis in term infants without symptoms born to mothers receiving intrapartum antibiotics and to determine the usefulness of the immature neutrophil: total neutrophil (I:T) ratio in the initial evaluation of these infants. A retrospective chart review was made of 103 infants born during a 3-year period. There was one positive blood culture and two positive cerebrospinal fluid cultures in three different patients; all three isolates were considered contaminants and all patients remained without symptoms. In spite of the lack of culture-proved sepsis and clinical illness, more than 50% of the initial I:T ratios were greater than the usually accepted upper limit of normal (that is, 0.16). We conclude that the incidence of sepsis in this population is very low and the initial I:T ratio is not useful as a predictive tool in term newborns without symptoms.

Parental recall of infant medical complications and its relationship to delivery method and education level.

Since relatively little is known as to why parents find it difficult to recognize when their high-risk infant ceases to be ill, this investigation examined parental reports of infant complications and the relationship these reports had with parental education level and method of delivery. Using a questionnaire format, 60 parents reported complications their infants experienced during NICU (neonatal intensive care unit) hospitalization. Maternal and paternal reports were comparable, although both significantly differed from actual diagnoses; parents underreported their infant's complications. Reported complications were not related to parental education level but were associated with method of delivery. Parents of Caesarean-section (C-section) infants identified a significantly smaller percentage of complications than did parents of vaginally delivered babies. It is suggested that (1) medical caregivers have the potential for helping parents more fully comprehend infant complications, (2) supplemental communication methods may be necessary for the task in (1), and (3) information communicated to parents may need to incorporate the current findings about parental education level and delivery method.

Nitrogen flux across ovine maternal and fetal hindquarters during fasting.

Nitrogen flux across the hindquarters of fetal and maternal sheep (n = 15) was determined during normal feeding and following 5 days of maternal fasting. Arterial and venous whole blood concentrations of free amino acids, ammonia and oxygen were measured entering and exiting the hindquarters. Further, the DNA, protein and nitrogen contents of the hindlimb skeletal muscle of the fetus were determined in the fed state and following the 5-day fast. Results of these studies indicate that maternal and fetal hindlimb metabolism differ during fasting. There is a net efflux of alanine, glutamine and total nitrogen from the maternal hindquarters following 5 days of fasting. The fetus also releases glutamine and alanine from the hindquarters during the fast, presumably as potential energy substrate. However, nitrogen balance across the fetal hindquarter remains positive as a result of increased positive arteriovenous differences for other amino acids (particularly leucine and isoleucine). The concentrations of DNA, protein and nitrogen in fetal skeletal muscle remain unchanged during fasting. These data indicate that, whereas the mother undergoes protein catabolism and net nitrogen loss from the hindquarter during fasting, the fetus maintains a positive nitrogen balance across the hindquarter.

Changes in ovine fetal hindlimb amino acid metabolism during maternal fasting.

The flux of various substrates across the ovine fetal and maternal hindlimbs was measured in the fed state and after 5 days of maternal fasting. Whole blood concentrations of glucose, oxygen, ammonia, and six amino acids (glutamate, glutamine, alanine, valine, isoleucine, and leucine) were determined in the fetal and maternal femoral artery and distal inferior vena cava in 15 chronic animal preparations. During fasting the fetal arterial glucose concentration fell by 40% (from 0.828 to 0.494 mM), and the arteriovenous concentration difference decreased by 30% (from 0.148 to 0.099 mM). Similar changes were noted in maternal blood. Fetal oxygen concentrations remained similar between the fed and fasted state, and the fetal arteriovenous oxygen concentration difference increased slightly from 0.861 to 1.02 mM. The glucose oxygen quotient decreased in the fetus from 1.20 to 0.621. In addition, significant changes occurred in the net balance of several amino acids during the fasted state. Both alanine and glutamine, which demonstrated a positive uptake by the fetal hindlimb during the fed state, showed a substantial efflux from the fetal hindlimb during the fasting period. The fetal arteriovenous concentration difference of the branched-chain amino acids (leucine, isoleucine, and valine) increased significantly during fasting. These observations are consistent with the hypothesis that the ovine fetus adapts to a diminished supply of glucose from the mother by enhanced amino acid catabolism and, possibly, proteolysis with subsequent release of gluconeogenic precursors in the form of alanine and glutamine.

Effect of pH on fecal recovery of energy derived from volatile fatty acids.

We assessed the effect of pH on volatilization of short-chain fatty acids during lyophilization. Acetic, propionic, valeric, and butyric acids were added to a fecal homogenate in amounts sufficient to raise the energy density by 18-27%. Fecal homogenate samples were either acidified (pH 2.8-3.2), alkalinized (pH 7.9-8.7), or left unchanged (4.0-4.8) prior to lyophilization and subsequent bomb calorimetry. Alkalinizing the fecal samples prevented the 20% loss of energy derived from each of these volatile fatty acids observed in samples either acidified or without pH adjustment. These data suggest that in energy balance studies involving subjects with active colonic fermentation, fecal samples should be alkalinized prior to lyophilization and bomb calorimetry.