Paul Y K Wu

Use of Fetal Ultrasound to Select Metabolic Therapy for Pregnancies Complicated by Mild Gestational Diabetes

OBJECTIVE To determine whether fetal ultrasound early in the third trimester can identify Latina with mild gestational diabetes mellitus (GDM) whose fetuses are at risk for macrosomia and, if so, whether maternal insulin therapy can reduce that risk. RESEARCH DESIGN AND METHODS Study subjects included 303 consecutive women with GDM and a fasting serum glucose level <5.8 mM on diet therapy who had a fetal ultrasound between 29 and 33 weeks gestation. Of the women, 98 (32%) had a fetal AC ≥ 75th percentile for gestational age, and 59 women completed a randomized trial of diet therapy (n = 29) or diet plus twice daily insulin (n = 30). Maternal nutrient levels were assessed by meal tolerance testing (MTT) before and during therapy and by capillary glucose monitoring four to seven times a day. Birth weights corrected for gestational age and neonatal glycemia and skin folds were the primary outcome variables compared between treatment groups. RESULTS Diet and diet-plus-insulin groups were well matched for maternal age, prepregnancy relative weight, weight gain during pregnancy, and glycemia at entry. Insulin therapy reduced maternal capillary (P < 0.005) and MTT (P < 0.001) glucose levels and prevented a diet-associated rise in MTT triglyceride levels (P < 0.002). Gestational age at delivery was similar in insulin- and diet-treated groups (39.6 ± 0.2 vs. 39.5 ± 0.2 weeks). Birth weights (3,647 ± 67 vs. 3,878 ± 84 g; P < 0.02), the prevalence of large-for-gestational age infants (13 vs. 45%, P < 0.02), and neonatal skin-fold measurements at three sites (P < 0.005) were reduced in the insulin-treated group. Rates of transient neonatal hypoglycemia were low in both treatment groups (14 and 18%, respectively) and didnot differ significantly between groups. CONCLUSIONS Fetal ultrasound early in the third trimester identified women with mild GDM whose infants were at high risk for fetal macrosomia in the absence of standard glycemic criteria for insulin therapy. Insulin treatment reduced the macrosomia, indicating that fetal ultrasound can be used to guide metabolic therapy in pregnancies complicated by mild GDM.

Perinatal factors and neonatal morbidity in twin pregnancy.

There were 177 pairs of twins reviewed. The incidence of twin pregnancy was 1:112.2 deliveries in a population consisting of 76.8 per cent Mexican-Americans. The incidence of breech, cesarean section, and assisted deliveries was higher in twins than singleton deliveries, and the incidence was higher in twin 2 than twin 1. Mortality rates, fetal and neonatal, were lower than those previously reported. Neonatal findings and complications include low Apgar scores, small-for-dates infants, hyaline membrane disease, hypoglycemia, hypocalcemia, hyperbilirubinemia, and congenital malformation. The increased incidence of deaths and morbidity in twin pregnancy, as compared to singleton pregnancy, was attributed to prematurity, and to complications and diseases pertaining to prematurity, rather than to twinning per se.

Cardiac output in newborn infants with transient myocardial dysfunction

Decreased cardiac output is a common presumption in left ventricular myocardial dysfunction in neonates, but because of a lack of reliable noninvasive techniques, data on cardiac output are missing. We measured cardiac output by pulsed Doppler echocardiography in 22 newborn infants with left ventricular myocardial dysfunction diagnosed by M-mode echocardiography. Eleven neonates had severe perinatal asphyxia, seven had tachypnea, two hypoglycemia, and one septic shock; one had no symptoms. Right ventricular function was abnormal in 13 of the 22 infants. Hypotension was found in eight; cardiac output and stroke volume were low in 20. The abnormalities were more pronounced in infants with asphyxia. Six such infants were given dopamine (4 to 10 micrograms/kg/min). Within 1 hour, arterial blood pressure, cardiac output, stroke volume, and heart rate increased sharply, with normalization of the myocardial contractility; the other echocardiographic abnormalities normalized over 24 to 48 hours. Pulsed Doppler echocardiography is an advance in the detection and evaluation of therapy for left ventricular myocardial dysfunction in the neonate.

Plasma amino acid pattern in normal term breast-fed infants

It seems reasonable that amino acid solutions used for parenteral nutrition should lead to a plasma amino acid pattern that resembles that of the normal, postprandial concentrations of amino acids in breast-fed infants. Previous studies of postprandial plasma amino acid concentrations have been inadequate for several reasons, such as consumption of infant formulas of different composition, inadequate intake of human milk, varying times of postprandial plasma sampling, a wide range of infants studied, and incomplete data sets lacking one or more nutritionally important amino acids? -4 Our study was designed to obtain complete plasma amino acid data for the breast-fed infant. It has been suggested that this normal plasma amino acid pattern represents the optimal pattern for supporting growth, and possibly for estimating repletion of the nutritionally compromised patients. METHODS Subjects were infants of multiparous women 15 to 28 years of age (mean 22.9 years), 20 Hispanic and one black, who met the following entry criteria: mothers of normal nutriture as assessed by using appropriate weight and height charts; term neonates appropriate for age, with normal weight/length ratio using the ponderal index of Miller and HassaneinS; both mothers and infants healthy; informed consent; infants exclusively breast-fed during the first month of life. This study was approved by the Research Committee of the Los Angeles County-University of Southern California Medical Center and the USC School of Medicine.

Geometry of neonatal and adult red blood cells.

Summary: Red blood cell (RBC) geometry is a determinant of RBC deformability, survival time, osmotic resistance, and oxygen uptake. Because accurate information on the geometry of neonatal RBC appears lacking, a micropipette technique was employed to measure surface area and volume of individual neonatal and adult RBC. In addition, RBC diameter was determined microscopically. From these measurements, surface area index (actual surface area divided by area of sphere of same volume), swelling index (maximal volume divided by actual volume), minimum cylindrical diameter and mean thickness of RBC were calculated. Compared to adult cells, the volume of neonatal RBC was 21% larger, their surface area was 13% greater and their diameter 11% wider. The surface area-to-volume ratio of the neonatal RBC was 1.42 ± 0.08 and that of the adult RBC was 1.49 ± 0.06 (P <0.05). The minimum cylindrical diameter of the neonatal RBC was 3.04 ± 0.25 μm and that of the adult RBC was 2.81 ± 0.23 μm (P <0.05). Mean RBC thickness, surface area index and swelling index were not significantly different.

Medium-chain triglycerides in infant formulas and their relation to plasma ketone body concentrations

ABSTRACT. A mild ketosis is known to prevail in the mother, fetus, and newborn infant during the 3rd trimester and in the early neonatal period. It has been shown that during an equivalent period in the rat ketone bodies are readily oxidized and serve as key substrates for lipogenesis in brain. Since medium-chain triglycerides are known to be ketogenic, preterm infants may benefit from dietary medium- chain triglycerides beyond the point of enhanced fat absorption. Our objective was to determine the ketogenic response in preterm infants (gestational age: 33 ± 0.8 wk) fed three different isocaloric formulas by measuring the concentrations of 3-hydroxybutyrate and acetoacetate in the plasma of these infants. At the time of entrance to the study the infants were receiving 110 kcal/kg/24 h. Study I (11 infants): the infants were fed sequentially in the order; PM 60/40 (PM), Special Care Formula (SCF), and Similac 20 (SIM). In SCF greater than 50% of the fat consists of medium-chain length fatty acids while PM and SIM contain about 25%. The concentration of 3-hydroxybutyrate in plasma was significantly higher when infants were fed SCF than PM and SIM [0.14 ± 0.03, 0.06 ± 0.01, and 0.05 ± 0.01 mM, respectively (p< 0.01)]. Study II (12 infants); the infants were fed SCF, then SIM, or the reverse. The concentration of acetoacetate in plasma was 0.05 ± 0.01 and 0.03 ± 0.01 mM when infants were fed SCF and SIM, respectively (0.1>p> 0.05). The concentrations of 3-hydroxybutyrate in plasma were similar to those measured in study I for the respective formulas. The increased plasma levels of 3-hydroxybutyrate and total ketone bodies when SCF was fed indicate that SCF promotes a mild ketosis in preterm infants similar to that reported in breast-fed term infants.

Peripheral Blood Flow in the Neonate. 1. Changes in Total, Skin, and Muscle Blood Flow with Gestational and Postnatal Age

Summary: Total peripheral blood flow and blood flow through the skin and muscle were measured in the calf with an electrocapacitance plethysmograph with counter pressure in a group of 62 “well” newborn infants (birth weight, ≤3500 g). Blood pressure in the contralateral leg was measured with an Arteriosonde 1010, and peripheral vascular resistance was calculated as mean blood pressure (mm Hg) divided by blood flow (ml per 100 ml tissue per min). The results show that total peripheral blood flow and blood flow through the skin and muscle correlated inversely with increasing birth weight and gestational age. Postnatally, total blood flow and blood flow through the skin and muscle decreased gradually during the first 7 days of life and in the rest of the neonatal period. Peripheral vascular resistance and resistance in the skin and muscle correlated directly with increasing birth weight and gestational age. Postnatally, peripheral vascular resistance and resistance in the skin and muscle increased during the first 7 days of life and the neonatal period.Speculation: The lower peripheral vascular resistance and hypervascularity in the skin of immature infants account for higher peripheral blood flow in these infants. The associated increment in peripheral vascular resistance account for the gradual decrement in periphera1 blood flow with advancing maturity and postnatal age. Differences in change of total peripheral blood flow and blood flow in the skin and muscle in relation to change in state, environment, and biochemical alterations need to be studied.

Colloid osmotic pressure: Variations in normal pregnancy

Pregnancy is associated with an increase in the extravascular fluid by about two litres. The regulation of fluid flux across capillary membrane is dependent on the STARLINGs forces. Thus increased fluid shift into the extravascular space may occur during pregnancy when the intra-capillary hydrostatic pressure exceeds the opposing influence of plasma colloid oncotic pressure (COP). In order to evaluate these forces more fully, COP, hematocrit (HCT), serum total solids (STS), mean blood pressure (MBP) and MBP-COP gradient (M-C) were measured cross-sectionally in 184 women with normal uncomplicated pregnancy. COP fell gradually during the first and second trimesters, lowest at 30-34 weeks, thereafter it rose. The relationship of COP and gestational age was best described by the quadratic equation. The patterns of changes of HCT and STS with respect to gestational age were similar to COP. MBP and M-C were linearly correlated to gestational age. The increment in M-C with advancing gestational age would promote fluid flux from intra to extravascular space in normal pregnancy.

Changes in Blood Flow in the Skin and Muscle with Phototherapy

Extract: The electrocapacitance plethysmograph with local counterpressure was adapted for measurement of total blood flow and blood flow through the muscle and skin in 20 icteric preterm infants. Measurements were recorded from each infant, before and during phototherapy. In 10 infants in study I, the incubator was set to maintain skin temperature of 36.5° initially and during phototherapy and no attempt was made to alter the incubator settings. Total blood flow was found to increase by a mean of 116% due primarily to increased skin blood flow (224%) and to a lesser extent, muscle blood flow (35%). Concomitant increases in heart rate, respiration rate, skin and incubator temperature were found, but no change was observed in rectal temperature. In 10 infants in study II, the skin temperature was kept constant at 36.5° before and during phototherapy by adjustment of incubator temperature. Significant increases, but of lesser magnitude, were observed in skin (52%) and total blood flow (37%), whereas muscle blood flow remained unchanged. Rectal temperature fell by a mean of 0.6° and respiration rate and heart rate remained unchanged.Speculation: During phototherapy both an increase in surface temperature and the direct effect of light results in augmentation of total blood flow. Increasing skin temperature appears to affect blood flow in both skin and muscle, whereas the direct effect of light from phototherapy lamps appears to affect skin blood flow only and to a lesser degree. The augmentation in skin blood flow should increase the efficiency of phototherapy. However, in small or sick infants the metabolic demands due to increasing temperature may outweigh any benefit from increasing blood flow.

Red blood cell aggregation in preterm and term neonates and adults.

ABSTRACT: Aggregation of red blood cells (RBC) is a major determinant of blood viscosity and of blood circulation through vessels with slow flow (i.e. veins). RBC aggregation and plasma fibrinogen were studied in placental blood samples from 25 neonates with 24 to 41 wk of gestation and in blood from 13 normal adults. The rate and final extent of RBC aggregation were measured by means of a rheoscope (increase in light transmission during blood stasis). Both the rate and extent of RBC aggregation were low in the premature infants, increased with gestational age, and reached the highest values in the adults. Blood from seven infants with 24 to 28 wk of gestation did not show any significant RBC aggregation during the first minute of stasis. RBC aggregation was closely related to the fibrinogen level. Cross-suspension studies (neonatal RBC in adult plasma and adult RBC in neonatal plasma) showed that neonatal and adult RBC had the same aggregation pattern when they were suspended in the same plasma. Moreover, neonatal and adult RBC demonstrated the same strong aggregation when they were resuspended in 1% dextran. These results indicate that specific plasma properties are responsible for the decreased RBC aggregation observed in the neonates while their specific RBC properties do not affect RBC aggregation.