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To describe total bilirubin production in healthy term infants, we measured the end-tidal breath CO, corrected for ambient CO (ETCOc), with an automated sampler and electrochemical (EC) CO instrument. For infants of mothers with a negative Coombs' test, the ETCOc was 1.3 +/- 0.7 microL/L (n = 397) and the serum bilirubin on day 3 postpartum was 73 +/- 35 mg/L (n = 381). In contrast, the ETCOc for infants with ABO or Rh incompatibility, a positive direct Coombs' test, and bilirubin > 130 mg/L (n = 9) was significantly higher, 1.8 +/- 0.8 microL/L, than for those who had a positive Coombs' test result but whose bilirubin was < or = 130 mg/L (n = 12), 1.0 +/- 0.5 microL/L (P < 0.05). At 2 to 8 h postpartum seven term babies from mothers with insulin-dependent diabetes had ETCOc of 1.8 +/- 0.7 microL/L, significantly higher than that in the other term infants [1.3 +/- 0.7 microL/L (n = 390), P < 0.04]. Their bilirubin concentration at 72 +/- 12 h was also higher: 121 +/- 45 mg/L (n = 7) vs 73 +/- 34 mg/L (n = 374; P = 0.03). We conclude that ETCOc measurements may be helpful in understanding the mechanisms of jaundice in healthy term infants in a variety of conditions.

The objective of this study was to determine whether the cumulus oophorus cells surrounding the human oocyte release a factor(s) that stimulates sperm velocity. Medium from in vitro fertilization (IVF) that was exposed to cumulus/oocyte complexes was tested for its ability to stimulate sperm velocity by use of a computerized sperm motion analyzer. In subsequent experiments, primary cultures of cumulus cells, granulosa cells, and ovarian cancer cells were established, and conditioned medium from these cells was assessed for sperm velocity-stimulating activity. In the initial series of assays using four sperm donors, cumulus/oocyte complex-conditioned medium from IVF increased sperm curvilinear velocity and amplitude of lateral head displacement by an average of 12.3% and 19.3% (p < 0.0001), respectively, compared to medium from IVF that was not exposed to cumulus/oocyte complexes. These results were confirmed in a subsequent, more extensive series of assays using a single sperm donor. Testing of conditioned media after 24 h of primary cell culture showed that cumulus-conditioned medium consistently stimulated curvilinear velocity (8.8% increase) and lateral head amplitude (18.7% increase) compared to unconditioned medium (p < 0.0001) in a manner similar to cumulus/oocyte complex-conditioned medium. In contrast, granulosa-conditioned medium and ovarian cancer cell-conditioned medium did not stimulate curvilinear velocity and lateral head amplitude compared to unconditioned medium. The ability of cumulus-conditioned medium to stimulate curvilinear velocity and lateral head amplitude declined gradually during the 5-day culture period. Nevertheless, the results indicate that the cumulus released velocity-stimulating activity throughout the culture period.(ABSTRACT TRUNCATED AT 250 WORDS)

Follicular fluid alters the physiology and behaviour of spermatozoa by increasing acrosome reaction, accelerating capacitation, attracting the spermatozoon and enhancing vigorous motion of the cell. The objective of this study was to characterize the factor(s) in human follicular fluid that causes vigorous spermatozoa motion. Follicular fluid and its fractions were tested for stimulation of spermatozoa motion using a standardized assay which employs a computerized digital imaging system. Our results show that both follicular fluid and its methanol extract stimulate vigorous spermatozoa motion. To determine the characteristics of the active factor(s), the methanol extract was subjected to molecular weight fractionation, protease digestion, microcrystalline thin-layer chromatography (TLC) and C18 reverse-phase high-pressure liquid chromatography (HPLC). The spermatozoa motion stimulator in the methanol extract was dialysable against a low molecular weight membrane (1000 Da), insensitive to boiling and low pH (3.5) and was largely inactivated by proteinase K digestion. The activity was detected near the solvent front on TLC. Using reverse-phase HPLC monitored at 254 nm (UV), the activity eluted as a single peak of activity at low methanol concentration, indicating that the activity was relatively hydrophilic. The activity in the HPLC peak lost most of its motion-stimulating ability after digestion with proteinase K. The motion stimulator could be a peptide analogous to the egg-associated peptides characterized in echinoderms which stimulate spermatozoa motion, respiration and chemotaxis.

Background: Nosocomial infections are a major cause of morbidity and mortality in premature infants. As a rule, their low serum gamma globulin levels at birth subsequently decline to hypogammaglobulinemic values; hence, prophylactic administration of intravenous immune globulin may reduce the rate of hospital-acquired infections., Methods: In this prospective, multicenter, two-phase controlled trial, 2416 infants were stratified according to birth weight (501 to 1000 g and 1001 to 1500 g) and randomly assigned to an intravenous immune globulin group (n = 1204) or a control group (n = 1212). Control infants were given placebo infusions during phase 1 of the study (n = 623) but were not given any infusions during phase 2 (n = 589). Infants weighing 501 to 1000 g at birth were given 900 mg of immune globulin per kilogram of body weight, and infants weighing 1001 to 1500 g at birth were given a dose of 700 mg per kilogram. The immune globulin infusions were repeated every 14 days until the infants weighed 1800 g, were transferred to another center, died, or were sent home from the hospital., Results: Nosocomial infections of the blood, meninges, or urinary tract occurred in 439 of the 2416 infants (18.2 percent): 208 (17.3 percent) in the immune globulin group and 231 (19.1 percent) in the control group (relative risk, 0.91; 95 percent confidence interval, 0.77 to 1.08). Septicemia occurred in 15.5 percent of the immune globulin recipients and 17.2 percent of the controls. During phase 1 the rate of nosocomial infections was 13.4 percent in the immune globulin group and 17.8 percent in the control group; the respective rates during phase 2 were 21.0 percent and 20.4 percent. The predominant organisms included gram-positive cocci (53.0 percent), gram-negative bacilli (22.4 percent), and candida species (16.0 percent). Adverse reactions were rarely observed during the infusions. Immune globulin therapy had no effect on respiratory distress syndrome, bronchopulmonary dysplasia, intracranial hemorrhage, the duration of hospitalization, or mortality. The incidence of necrotizing enterocolitis was 12.0 percent in the immune globulin group and 9.5 percent in the control group., Conclusions: Prophylactic use of intravenous immune globulin failed to reduce the incidence of hospital-acquired infections in very-low-birth-weight infants.

This report describes the neonatal outcomes of 1765 very low birth weight (less than 1500 g) infants delivered from November 1987 through October 1988 at the seven participating centers of the National Institute of Child Health and Human Development Neonatal Intensive Care Network. Survival was 34% at less than 751 g birth weight (range between centers 20% to 55%), 66% at 751 through 1000 g (range 42% to 75%), 87% at 1001 through 1250 g (range 84% to 91%), and 93% at 1251 through 1500 g (range 89% to 98%). By obstetric measures of gestation, survival was 23% at 23 weeks (range 0% to 33%), 34% at 24 weeks (range 10% to 57%), and 54% at 25 weeks (range 30% to 72%). Neonatal morbidity included respiratory distress (67%), symptomatic patent ductus arteriosus (25%), necrotizing enterocolitis (6%), septicemia (17%), meningitis (2%), urinary tract infection (4%), and intraventricular hemorrhage (45%, 18% grade III and IV). Morbidity increased with decreasing birth weight. Oxygen was administered for greater than or equal to 28 days to 79% of less than 751-g birth weight infants (range between centers 67% to 100%), 45% of 751- through 1000-g infants (range 20% to 68%), and 13% of 1001- through 1500-g infants (range 5% to 23%). Ventilator support for greater than or equal to 28 days was given to 68% of infants at less than 751 g, 29% at 751 through 1000 g, and 4% at greater than 1000 g. Hospital stay was 59 days for survivors vs 15 days for infants who died. Sixty-nine percent of survivors had subnormal (less than 10th percentile) weight at discharge. The data demonstrate important intercenter variation of current neonatal outcomes, as well as differences in philosophy of care and definition and prevalence of morbidity.

Retinal function was assessed by electroretinogram in 32 neonates randomly assigned to formulas of different omega-3 fatty acid content and in 10 infants fed human milk. All neonates had a birth weight of 1000-1500 g and were fed study diets from d 10 to 45 or discharge. Group A received formula containing predominantly 18:2 omega-6. Group B received a balanced mix of 18:2 omega-6 and 18:3 omega-3. Group C was given a formula containing both essential fatty acids and supplemented with marine oil to provide 22:6 omega-3 content similar to that of human milk. The fatty acid composition of plasma and red blood cell (RBC) lipids were similar for all groups on entry but marked diet-induced differences were found after feeding the study diets. Group C was comparable to the human milk-fed group, but group A had lower 22:6 omega-3 and omega-3 long-chain polyunsaturated fatty acids (LCPUFA) in plasma and RBC membranes. Cone function was not affected by dietary essential fatty acids. Rod electroretinogram thresholds were significantly higher for group A relative to the human milk-fed group and group C and significantly correlated with RBC omega-3 LCPUFA (r = -0.63, p less than 0.0001); 44% of the variance could be explained by RBC and plasma omega-3 LCPUFA content.(ABSTRACT TRUNCATED AT 250 WORDS)

To obtain growth data on a large sample of low birth weight preterm infants, we monitored 608 infants longitudinally in an eight-site collaborative program. Ninety-nine infants weighed less than or equal to 1250 gm at birth, 289 between 1250 and 2000 gm, and 220 infants between 2000 and 2500 gm. Thirty-four percent were white, 52% black, and 14% Hispanic. Weight, height, and head circumference were measured at birth and at 40 weeks and 4, 8, and 12 months of gestation-corrected age on at least 553 infants each time. Descriptive statistics for all growth variables and a body mass index (kilograms per square meter), plotted by sex and birth weight group, demonstrated growth patterns lower than published standards for term infants of the same age and sex. These patterns of growth differed by birth weight group. No catch-up growth was noted by the 12-month examination (gestation-corrected age) for any birth weight group. We conclude that low birth weight preterm infants have different patterns of growth than term infants during the first year of life, even with plotting corrected for gestational age.

The concentrations of insulin-like growth factors I and II (IGF-I and IGF-II) in amniotic fluid were determined by specific immunoassays in 58 women. IGF-I concentrations were constant throughout gestation at approximately 20 ng/ml; the mean IGF-II concentration was 114 +/- 13 (+/- SE) ng/ml at the earliest period of gestation studied and remained unchanged at 26 to 33 weeks despite a greater than 50% decrease in amniotic fluid total protein. A precipitous decrease in IGF-II concentration occurred at term which was not explainable by alterations in total amniotic fluid protein concentration. The concentrations of IGF-I and IGF-II in amniotic fluid did not correlate with concentrations of these factors in maternal serum (r = 0.08 and 0.09, respectively). [125I]IGF-I and [125I]IGF-II, after incubation with amniotic fluid, bound to a 40-45 K protein (or proteins). A carrier protein of greater mol wt, as in serum, was not detected. These findings indicate that there is dynamic control of IGF in amniotic fluid during normal pregnancy.

The high concentrations of prolactin (hPRL) in human amniotic fluid appear to be derived principally from maternal decidua. The present study evaluated both the biologic and immunologic activity of amniotic fluid hPRL obtained from normal and selected complicated pregnancies. Biologic and immunologic activities of amniotic fluid hPRL were also compared with lecithin:sphingomyelin ratios and phosphatidylglycerol content. No significant correlation existed between amniotic fluid hPRL activities and fetal lung maturation. However, a significant increase in amniotic fluid hPRL concentration as well as specific biologic activity of the hormone was found in pregnancies complicated by hypertension. These findings suggest alterations in the synthesis of decidual hPRL and/or its transport to the amniotic fluid that may influence pregnancy-induced hypertension.

Tachycardia in both fetuses of a twin gestation was documented in a mother who had undergone subtotal thyroidectomy 8 years prior to her present pregnancy. Maternal and fetal plasma concentrations of long-acting thyroid stimulator (LATS) and amniotic fluid 3,3',5'-triiodothyronine (reverse T3) were determined. All values were consistent with the diagnosis of fetal thyrotoxicosis, as were cord blood studies performed on the fetuses post partum. Significant concentrations of LATS were present in fetal cord blood. The first fetus survived but suffered hyperthyroidism during the first 3 neonatal weeks. The second twin died, possibly of fetal thyrotoxicosis. These studies suggest that in women with a history of thyrotoxicosis, high levels of maternal LATS may in some instances provoke fetal thyrotoxicosis, which can be diagnosed by the measurement of amniotic fluid reverse T3.

The theory of human decidualized endometrium to produce prolactin (PRL) throughout gestation has led to the implication that such production is related to the source of amniotic fluid PRL (afPRL). This study confirms that fetal membranes, amnion and amniochorion with or without adherent decidua, are unable to transfer significant quantities of exogenously administered PRL from the maternal to fetal compartments in vitro. Incubation of amniochorion with decidua adherent to chorion results in a significant increase in the amount of endogenous PRL appearing on the fetal side of the membrane concomitant with a rise in decidual PRL on the maternal side. The results suggest that transport of decidual PRL to amniotic fluid is predicated on retention of the cellular adhesion between maternal decidua and fetal chorion as exists in vivo. Disruption of decidual contact with fetal membrane results in failure of PRL transport to the fetal side despite a steady accumulation of PRL on the maternal side. We conclude that human fetal membranes are highly permeable to decidual PRL in vivo, and that decidua probably represents the major source of afPRL.

The relative validities of three clinical assessment methods for estimating gestational age in newborn low birth weight infants were evaluated with reference to estimates based on the date of the mother's last menstrual period. For 1246 infants in eight diverse institutions, estimates based on physical criteria correlated more strongly with dates estimates, yielded estimates more similar on average to dates estimates, and yielded higher proportions of correct classifications of prematurity and small for gestational age than did estimates based on neurologic criteria or neurologic and physical criteria combined. These results support the use of physical criteria rather than neurologic or combined criteria for the clinical assessment of gestational age in low birth weight infants. In a subsample of 511 black and white infants, there were no ethnic differences in mean error of estimate for any of the three methods.

The addition of ovine prolactin (oPRL) to the fetal side of human term amnion in vitro is associated with a decrease in membrane permeability to tritiated water (THO). As the concentration of oPRL is increased from 2.5 to 20.0 micrograms per milliliter, permeability is progressively impaired. The addition of a specific prolactin receptor antibody completely abolished the effect of oPRL. Also, the addition of Ouabain abolished the effect of oPRL. When an osmolic gradient was created using Dextran-10 on the maternal side of the amnion, the bulk flow of water in control and 3PRL-treated membranes was not significantly different. These findings suggest that PRL acts predominantly on the diffusional flow rather than the bulk flow of water across amnion and that it is a transcellular transport. These studies also represent indirect evidence for the existence of prolactin receptor sites at the level of the amnion.

During a 72 hour fast in pregnant women, significant decrements in the maternal plasma glucose concentrations, accompanied by a significant increase in the plasma placental lactogen (hPL) concentration, occur. At the same time, utilization of glucogenic amino acids, principally alanine, takes place. The mean postprandial glucose concentration in pregnancy is significantly lower than that of comparable nonpregnant women (70.5 +/- 1.7 versus 79.5 +/- 1.3 mg. per 100 ml., p less than 0.001). There appears to be a significant sparing effect on the maternal plasma glucose concentration during acute fasting which may be mediated through hPL. Concentrations of amniotic fluid and fetal plasma glucose from women undergoing fasting decrease in a manner parallel to that of the mother. Fasting provokes a mean rise in plasma hPL of 33.2 per cent over basal levels. This rise is still evident 72 hours after refeeding, after which it gradually returns to pretest concentrations. The infusion of alanine or arginine to pregnant women at the end of the fast produced increments in the peripheral maternal glucose concentration. The response was much greater with alanine than with arginine, demonstrating the increased gluconeogenic potential of this amino acid. The increment in human growth hormone (hGH) following alanine infusion was significantly greater than that observed after arginine administration. Hypoaminoacidemia was present in nonpregnant and pregnant women in response to fasting, but the decline was greater in pregnancy. Acute fasting in the first half of gestation appears to produce significant alterations in carbohydrate metabolism evidenced by profound hypoglycemia, hypoinsulinemia, and hypoaminoacidemia. This maternal deficit can be reflected in fetal substrate concentrations. The effect of these changes on fetal growth and development is speculative at this time.

Obstetric findings in 89 healthy women were evaluated prospectively by one obstetrician unaware of menstrual history. With weekly examinations, fetal heart tones were audible by fetoscope at 17.1 +/- 1.1 weeks' gestation (mean +/- SD) and the fundus reached the umbilicus at 16.6 +/- 0.9 weeks. At 20 to 31 weeks, fundal height in centimeters equaled weeks' gestation (confidence interval: +/- 3 weeks). The accuracy of predicting delivery date from combined findings (SD: 11.4 days) approached that from reliable menstrual history (SD: 10.2 days). Gestational age at delivery minus the pediatric Dubowitz estimate was 0.4 +/- 1.7 weeks. Gestational age may be overestimated by up to six weeks by assuming that the fundus reaches the umbilicus or that fetal heart tones appear at 20 weeks. However, carefully derived obstetric estimates potentially may be more reliable than pediatric estimates.

Loss to follow-up is a major problem in indigent inner-city populations. We evaluated a large, well-described, inborn indigent population of high-risk infants (HRI) and control infants (CI) to assess possible selection biases in loss to follow-up at one year adjusted age. Serial clinic visits, phone calls, and letters and payment of $20.00 for attending at 1 year was used to minimize patient loss. Yet, the 1 year loss rate was high, and among HRI, greater for ventilator-treated infants greater than 1500 g birthweight (71/114; 62%) than for ventilator-treated very-low-birthweight (VLBW; less than 1500 g) infants (39/108; 36%) or non-ventilated VLBW infants (62/145; 43%) (P less than 0.05). Multivariate analyses indicated that those lost to follow-up were at no greater risk of a poor outcome on the basis of prenatal and perinatal medical and socioeconomic findings than were those in the same risk group (HRI or CI) or subgroup of HRI who were examined at 1 year. In a review of hospital records, similar rates of hospitalization and neurologic problems during infancy were identified for HRI examined and HRI lost to follow-up. The identification of such morbidity during infancy may be less complete for HRI lost to follow-up than for those examined. Thus, the high frequency of deficits observed in follow-up evaluation of indigent HRI is unlikely to result from loss of unaffected infants.

Taurine may be important to the developing eye and brain of the small preterm infant. A blinded randomized trial was conducted to determine whether taurine supplementation of healthy infants of less than or equal to 1,300 g birth weight until their discharge from the hospital increases their growth rate, neurobehavioral development, electroretinographic development, or maturation of auditory brainstem-evoked responses. Infants were fed with Similac Special Care as desired, which was prepared to contain less than 5 mg/L of taurine or 45 mg/L of taurine, a concentration similar to that of human milk. Infants who did not receive taurine supplementation (n = 19) and those who did (n = 18) were similar with respect to condition at study entry, caloric intake, and growth rates throughout the study, and electroretinographic findings and scores on the Brazelton Behavioral Assessment Scale at 37 weeks' postmenstrual age. Infants who received taurine supplementation had greater overall plasma taurine concentrations. The group receiving taurine supplementation also had more mature auditory-evoked responses at 37 weeks' postmenstrual age with a modest (0.2 to 0.5 ms) but consistent reduction (P less than .05) in the interval between stimulus and response at two different stimulation rates. Although further study is needed, taurine intake appears to influence auditory system maturation of preterm infants.

Concentrations of prolactin in amniotic fluid, fetal plasma, and maternal plasma were determined in 34 rhesus monkeys delivered by hysterotomy under general anesthesia at gestational ages of 110 to 160 days (term, 165 days). Included were 15 cases (gestational ages 110 to 143 days) in which the mothers received 2 mg of betamethasone intramuscularly daily for 3 days prior to delivery. Fetal lung maximum volumes were determined in addition to the following indices of fetal lung surfactant: lung alveolar stability, lung phosphatidylcholine concentrations, lung extract surface tensions, and amniotic fluid lecithin to sphingomyelin ratios. Amniotic fluid prolactin was found to correlate significantly with lung alveolar stability (r = 0.51; p less than 0.01), lung phosphatidylcholine (r = 0.51; p less than 0.01), lung extract surface tension (r = -0.39, p less than 0.05) and amniotic fluid lecithin/sphingomyelin ratio (r = 0.50; p less than 0.01). These correlations remained statistically significant even when the effects of gestational age were taken into account. These findings suggest that amniotic fluid may modulate fetal production of surfactant via its prolactin content.

The hypothalamus exerts an inhibitory influence on prolactin release from the anterior pituitary. Whether or not peptide hypothalamic prolactin-regulating factors, analogous to those for other pituitary hormones, exist, remains to be confirmed. There is evidence that catecholamines and indolamines directly affect prolactin release. This concept may explain the pathogenesis of galactorrhoea-amenorrhoea and other endocrine diseases produced by hypothalamic-pituitary disorders.

The addition of human or ovine prolactin to the fetal side of the human amnion is associated with a latent decrease in membrane permeability. The specificity of this effect of prolactin is observed when equimolar concentrations of human placental lactogen and human growth hormone were used in place of ovine prolactin and failed to influence water transport. Likewise, the extracellular transport of p-aminohippurate across human amnion was unaffected by the addition of ovine prolactin. Tritiated water transport under these circumstances, however, remained impaired. The addition of antibody to ovine prolactin completely blocked the effect of this polypeptide on membrane permeability. Permeability to tritiated water remained unchanged when synthetic arginine vasopressin was added to the fetal side of the amnion. The results imply an active role for prolactin on water transport across human amnion. Moreover, the latent period between the addition of the polypeptide and its subsequent influence on permeability suggests a biologic effect of this hormone. That this effect is related to ion transfer remains to be shown.

Bank milk collected by manual expression was less likely to be contaminated than milk collected by other methods. Contamination with coliforms and gentamicin-resistant Gram-negative rods was related to the pumps used by donors in their homes. Stringent precautions reduced but did not eliminate contamination.

An increasing and consistent production of prolactin by decidual tissue (dhPRL) has been shown during a 24-hour incubation in a chemically defined buffer medium. No difference in dhPRL release was observed in tissue obtained from first- and third-trimester pregnancy. Estradiol had neither a stimulatory nor an inhibitory influence on dhPRL release, although release of this polypeptide by decidual tissue incubated with cycloheximide was blocked. The precise mechanism controlling the production and release of dhPRL is not known. Addition of theophylline, dibutyryl cyclic adenosine monophosphate, or guanosine triphosphate had no effect on dhPRL release during a 4-hour incubation. In contrast, these substances provoked a statistically significant increase in PRL release from rat hemipituitaries coincubated in vitro. Displacement curves for dhPRL against a human PRL standard suggest molecular homogeneity between both hormones. The biologic activity of dhPRL was next confirmed by means of a new bioassay system with a lower level of sensitivity of 20 pg/ml. In addition, dissociation of the biologic and immunologic activity of dhPRL has been completed and suggests that at least three isohormones are produced by human decidual tissue. The dhPRL production rate per gram of decidual tissue wet weight is far below that reported for the pituitary homologue. These studies not only provide confirmatory evidence of the immunologic and biologic activity of dhPRL but also intensify speculation as to its role in human gestation, including that related to osmoregulation across human amnion.

To study the effects of prolactin (PRL) on adrenocortical function in humans, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), androstenedione (delta) and testosterone (T) were measured in serum obtained from 35 hyperprolactinemic women with galactorrhea and amenorrhea before and after treatment with bromocriptine-induced fall in mean PRL levels from 82 +/- 8 (SE) to 14 +/- 2 ng/ml (n = 39, P less than 0.0005), DHAS fell from 322 +/- 21 to 237 +/- 21 microgram/dl (n = 39); P less than 0.0005), DHA fell from 492 +/- 47 to 378 +/- 30 ng/dl (n = 39; P less than 0.01) while T (n = 16) and delta (n = 13) levels were unchanges (44 +/- 4 vs. 49 +/- 4 ng/dl and 280 +/- 55 vs. 236 +/- 40 ng/dl, respectively). In addition, 4 women were infused iv with 25 microgram synthetic ACTH over 4 h and serial blood samples drawn while hyperprolactinemic, and again 2-4 months later following normalization of PRL levels by bromocriptine. Although pre-infusion levels of DHAS were lower when PRL levels were normalized, no significant differences in responses of circulating DHAS, DHA, T, cortisol and 17-hydroxyprogesterone concentrations were detected between the two infusions. Since DHAS is virtually an exclusive product of the adrenal cortex, and since high PRL levels appear to inhibit ovarian steroid production, the findings suggest that hyperprolactinemia selectively stimulates adrenocortical androgen production.

The activities of nurses, residents, and fellows providing newborn intensive care were studied by time-lapse photography. Six of 40 frames taken each hour during a 23-day period were evaluated. Time spent in bedside care, charting, handwashing, and other activities were estimated for personnel in a four-bed area. The amount of care prescribed for each infant was assessed independently by calculation of a care score from the physicians' orders. Physician activities were significantly diminished at night and on weekends. Bedside care given by physicians increased abruptly at high care scores. Total bedside nursing care was unaffected by time-related variables (day vs. night; weekday vs. weekend; nursing rotations). Regression analysis showed a linear two- to three-fold increase in bedside nursing time with increasing care score. Individual nurses differed significantly in mean time devoted to bedside care and in their response to increasing infant care score. Differences between nurses accounted for as much of the total variation in bedside care (30%) as did differences between infants in care needs. Many factors are likely to affect the individual or group performance of nursery staff. The traditional duty schedule for physicians is associated with a deterioration in their performance at night and the nocturnal increase in neonatal acidosis and mortality previously reported by the authors.

A prospective study of 70 singleton pregnancies at high risk for intrauterine growth retardation (IUGR) was undertaken to determine 1) the differences in intrauterine growth patterns; 2) the diagnostic accuracy of obstetric techniques; and 3) the frequencies of perinatal complications. Thirty infants displayed signs of IUGR. Although only 14 infants had low birth weights, these 14, as well as the remaining 16 infants under study, displayed many other features of growth abnormalities, including a low ponderal index, short stature, and small head circumference. These data demonstrate various patterns of IUGR. Although the perinatal complications occurred primarily in the low-birth-weight group, the major growth abnormalities observed in the non-low-birth-weight group demonstrate the need for additional short- and long-term follow-up studies in both groups.

The objective of management in the pregnant diabetic patient is to achieve physiologic glucose homeostasis through the use of diet and insulin. As outlined, the numerous ancillary tests developed during the past 15 years to assist the clinician in determining impending fetal death have left much to be desired, especially where metabolic homeostasis has not been achieved prior to the thirty-sixth week of gestation. The statistics from this institution indicate that the maintenance of the plasma glucose concentration below 100 mg. per cent throughout gestation, regardless of the severity of the diabetes, all but removes the risk of maternal-fetal complications due to diabetes. The management is uniform for all patients exhibiting an abnormality of carbohydrate metabolism, and, although it is rather difficult to accept, there have been minimal neonatal complications when the protocol outlined in this presentation has been followed.

Using both a homologous porcine RIA and 3 bioassays, we investigated the relaxin content of human decidua from first trimester and term gestations and of placentas at term. Aqueous extracts of these tissues yielded only between 211 and 1090 pg immunoreactive relaxin/g fresh tissue. Neither acetonehexane extraction, octadecylsilica cartridge elution nor molecular sieve chromatography increased these relaxin levels. Compared with term decidua, first trimester decidua contained significantly higher levels of immunoreactive relaxin. In vitro studies did not evidence significant relaxin production by either decidual or placental tissues, even in the presence of decidual prolactin production. These results are in direct contrast to earlier reports of high concentrations of relaxin in decidua and placenta.

Human amniotic epithelium has been found to consist of two cell types, known as dark and light cells, that are functionally different with respect to the passage of large molecules across the epithelium. Both cell types permit passage of ferritin intercellularly, whereas light cells incorporate this macromolecule. Dark cells impair the passage of 125I-PRL both inter- and intracellularly, whereas it is localized in light cells. In addition to a selectivity regarding the transmembrane passage of large molecules by the two cell types, we suggest that the osmoregulatory action of PRL on human amnion is restricted to the epithelial layer, and that its action may be mediated by light cells.

To determine if an effective method existed for distinguishing the physiologic hypoglycemia of fasting from pathologic hypoglycemia, 72-hour fasts were conducted in 60 women and 20 men of normal weight, in 16 obese subjects, and in six of 11 patient with insulinomas. Only the pattern of change of the immunoreactive-insulin-to-glucose ratio (the I/G ratio), calculated at major time intervals of the fast, provided a clear-cut distinction between these groups; plasma glucose values alone could not make this distinction. The mean fasting I/G ratio was calculated for each subject from that subject's I/G ratios at 12-hour intervals during the fasting period. In no single case did the mean I/G ratio during fasting for an individual of normal weight equal or exceed the control I/G. I/G ratios increased dramatically during fasting in each patient with an insulinomas. Normal obese patients (15% greater than ideal body weight) did not provide a diagnostic problem, since, regardless of sex, glucose values of less than 55 mg/dl. did not occur. Although the pattern of change of the I/G ratio was extremely useful, the basal I/G ratio alone was potentially misleading; this was due to overlap of basal I/G ratios between subjects with simple obesity and patients with insulinomas. In addition, absolute values for the I/G ratio varied with the technique employed for measuring glucose and insulin. Change of the I/G ratio, however, was independent of the techniques used for measuring glucose and insulin. DIABETES 26:161-65, March, 1977.

Severe catheter-related thromboatheromatous lesions were found at necropsy in 33 of 56 infants who had umbilical arterial catheters passed during life. In infants dying within 8 days of insertion of the catheter, varying degrees of thrombosis of the aorta and its major branches were seen. With increasing thrombosis and aging of the thrombus, fatty deposits were seen first within the thrombus, and then in the intima and media. In addition there was evidence of proliferation of medial smooth muscle cells and of disruption of the medial architecture below the thrombus, characterized by the presence of abundant mucopolysaccharide. In infants who survived longer, varying degrees of organization of the thrombus could be traced, leading eventually to raised fibrous plaques with lipid and occasionally calcification. The lesions in the older infants were similar in many respects to experimental thromboatheromatous lesions produced in rabbits, and to some lesions of artheroma occurring spontaneously in humans. A wide variety of embolic phenomena were found, with features suggesting asynchrony of embolic episodes. The presence of thrombotic lesions could not be related to birthweight, Apgar scores at 1 and 5 minutes, age at catheterization, duration of catheterization, underlying disease process, age at death or the presence of hypothermia, acidosis, or anomalies in coagulation tests. There is a need for less hazardous methods of monitoring arterial oxygen tension.

The elevation of endogenous prolactin secretion using thyrotopin releasing hormone was associated with significant increases in mammary milk production in postpartum women. More-over, a specific effect was seen on the percent fat composition which has been shown to rise as much as 228% over pretest conditions. As in the bovine, administration of high doses of estrogen is associated with mammary breast development and the sudden removal of this stimulus if accompanied by nipple stimulation is associated with non-puerperal lactation. The inhibitory effects of estrogen on the mammary cellular response to circulating prolactin has been deduced from studies in pregnant and parturient women by measuing the TRH-induced prolactin response. These studies support a relationship between prolactin and sex steroids on the initiation and maintenance of human lactation.

A 30-year-old man with a prolactin secreting pituitary adenoma and hypogonadism was studied. Except for hyperprolactinemia, the results of his pituitary function tests were perfectly normal. Although the mechanism is uncertain, hyperprolactinemia alone may interfere with male reproductive function. The patient's impotence and infertility were successful managed with injections of human menopausal gonadotropins (HMG). Adverse interaction between gonadotropins and prolactin along the hypothalamic-pituitary-testis axis may be corrected by HMG injections in certain cases.

To compare maternal-infant interactions in high- and low-risk groups, we observed infants who had required neonatal intensive care and otherwise similar infants with normal perinatal histories in a follow-up clinic at one year adjusted age. The developmental level as assessed by the Bayley Scales of Infant Development was significantly lower for the high-risk infants than for the control infants at one year of age. Principal component analyses were used to define interaction patterns in each of five situations. Principal component analyses allow a more meaningful analysis of interrelated maternal and infant behaviors than do standard statistical analyses and minimize the likelihood of misleading 'significant' findings resulting from multiple comparisons. Prior to being examined, mothers of control infants were more likely to adopt an 'en face' position, play with, comfort, talk to, and smile at their infants than were mothers of high-risk infants. Control infants were more likely to smile in return. These differences between control and high-risk mother-infant dyads disappeared when the infants' developmental level was statistically controlled. Group differences in maternal-infant interactions independent of the infants' developmental level were observed in only one situation (collection of blood). Specific medical risk factors had little relation to findings at one year. Maternal-infant interaction should be interpreted in relation to the postconceptional and developmental age as well as the postnatal age of the infant.

3 groups of high-risk newborns and their controls were assessed at 92 weeks post-conceptional age using Bayley's Infant Behavioral Record (IBR). The 3 groups of high-risk infants were those who weighed 1,500 grams or less at birth and required no ventilator therapy, those weighing 1,500 grams or less at birth who required ventilator therapy, and newborns weighing more than 1,500 grams at birth who required ventilator therapy. Controls were healthy term infants matched for 7 socioeconomic and demographic variables. The first principal component of the IBR ratings for the 3 groups of high-risk infants and the controls were similar. All 3 groups of high-risk infants received less desirable IBR ratings on most items than their controls. In addition, there were some differences among high-risk groups; ventilated infants regardless of birth weight received the lowest ratings reflecting overall performance on the IBR, very low birthweight, ventilated newborns were more likely to receive ratings characterizing an overly active infant with a short attention span, and very low birth-weight, never-ventilated infants were most likely to be rated as happy but passive and delayed. The differences between the high-risk infants and controls in large part resulted from infants who were also delayed in terms of their mental and motor development.

This study analyzes the morbidity of therapeutic abortion and identifies predisposing factors. A retrospective case evaluation of 2,105 pregnancy terminations was performed. Major complications occurred in 5% of those undergoing curettage procedures, 41% of women undergoing prostaglandin amnioinfusion, and 17% of those who had hysterotomy as a method of abortion. Age, parity, and history of previous pregnancy termination, had little effect on morbidity. Surgical/technical factors and reliance on amnioinfusion and hysterotomy as procedures of choice for pregnancy termination contributed significantly to the high morbidity rates. This contribution, however, was overshadowed by the influence of patient delay, physician delay, and limited abortion facilities, resulting in 35.4% of pregnancy terminations being performed in the midtrimester. Improvements in abortion technique may lower the incidence of complications, but the need for more appropriate facilities is emphasized.

Production of a biologically active prolactin by human decidual tissue and its influence on the permeability of amniochorion to water suggests a functional relationship between the polypeptide and fetal membrane metabolism. Under in vitro circumstances, we used ovine prolactin and the Ussing chamber technique to determine the role of prolactin in prostaglandin E2 production by human fetal membrane. Fresh reflected membranes obtained from elective cesarean sections were exposed to ovine prolactin (10 micrograms/ml). Aliquots of incubation media were sampled at 0, 30, 60, 120, and 240 minutes, quick-frozen, and later assayed for prostaglandin E2. Multifactorial analysis of variance revealed that ovine prolactin significantly reduced prostaglandin E2 production (f = 13.42, p less than 0.005). Prostaglandin E2 output was greatest by amnion (3581 +/- 596 pg/ml/gm declining to 1819 +/- 452 pg/ml/gm during 4 hours). Other combinations of fetal membranes including amnion-chorion-decidua produced only 12% to 15% prostaglandin E2 per gram compared with that produced by amnion alone. Those membranes similarly responded to prolactin with a reduction in prostaglandin E2 output of 34% to 59%. Correlation analysis identified a significant relationship between prostaglandin E2 production and time (r = 0.298; p less than 0.001), which was abolished by ovine prolactin (r = 0.115, p greater than 0.10). This model illustrates that ovine prolactin modifies the production of prostaglandin by fetal membranes in vitro. By analogy, endogenous prolactin by human decidual tissue might also inhibit the elaboration of prostaglandin E2 from its precursors residing within the fetal membranes.

The biological (BA) and immunological (IA) activities of human PRL have been determined in samples of decidual incubation medium, amniotic fluid, and maternal and fetal cord sera obtained from cesarean sections performed at term. PRL from each of the four compartments was assayed using the Nb2 node rat lymphoma cell line and homologous RIA. BA to IA ratios of PRL, when compared within and between compartments, indicate that the BA of PRL from each compartment is equivalent to that of its IA. Thus, the BA of PRL from decidual incubation medium and amniotic fluid was found not to differ from that of pituitary PRL. These data suggest that PRL produced by decidua and found in amniotic fluid is a biologically active hormone.

The effect of extra maternal-infant contact during the first postpartum hour on maternal perception of infant behavior one month after delivery was measured by the Broussard Neonatal Perception Inventories and the attachment questions of Klaus and colleagues. All mothers were indigent primiparas who vaginally delivered normal, term infants. 60 mother-infant dyads were randomly assigned to either an extra contact or routine contact group. 49 mothers were available 1 month later for home visits. Scores on the Neonatal Perception Inventories were not significantly affected by either degree of contact or the sex of the child. There was also no difference between contact groups in the maternal response to the attachment questions. Infant behaviors recorded by 24 mothers during the 4 days following home visits were similar in the 2 contact groups. Mothers reported significantly more negative behaviors for female than for male infants. Any effects of extra contact during the first hour after birth on maternal-infant interaction are unlikely to result from changes in maternal perception of infant behavior.

Physicians are often faced with conflicting recommendations from therapeutic studies. An evaluation form is proposed to facilitate the evaluation of the quality of therapeutic studies and the resulting treatment or management recommendations in any area of medicine. Twelve major topics for evaluation include sample size determination, randomization, selection of control group(s), "blinding," and support for treatment recommendations. Emphasis is placed on study design and performance rather than data analysis. Thirty-four primary criteria based on accepted research standards are designated as most important, and examples from the literature are provided to illustrate their use. The form provides a comprehensive set of well-accepted standards of research in a format that encourages detailed, consistent, and thoughtful evaluation of therapeutic studies. The evaluation form is recommended as a tool for physicians who wish to develop and exercise skill in evaluating therapeutic studies.

The purpose of this prospective study was to determine whether serial maternal venous hPL determinations could identify pregnancies resulting in growth-retarded infants from a selected population at presumed high risk for IUGR. Our results demonstrated that mean hPL levels in IUGR outcome pregnancies were significantly lower than normal after 33 weeks' gestation. Mean hPL was also lower in some pregnancies resulting in normal-weight neonates with abnormally low PI or short CHL, suggesting that these neonates, despite normal birth weight achievement, may represent previously unsuspected.

As evidence continues to accumulate supporting a specific effect of prolactin on the permeability of reflected fetal membranes to tritiated water, no information on the role of decidual prolactin in this process is available. Simulation of in vivo events was conducted with the use of isolated membrane preparations of human amnion or chorioamnion with adherent decidua. In the presence of ovine prolactin in equal concentrations on both sides of human amnion, membrane permeability (cm X 10(-4) X sec-1) was reduced from 1.52 +/- 0.16 to 1.18 +/- 0.07 (mean +/- SEM) from the fetal to the maternal surface. Permeability in the opposite direction was significantly increased from 1.15 +/- 0.10 to 1.39 +/- 0.08. No osmotic effect of ovine prolactin was noted. With the use of chorioamnion with adherent decidua, permeability was significantly reduced from the maternal to the fetal surfaces only when ovine prolactin bathed the maternal surface. These in vitro results may suggest that the accumulation of decidual prolactin at the choriodecidual interface in vivo supports bulk water flow across fetal membrane from the amniotic to the maternal compartments.

The effect of laminaria-induced cervical dilatation of plasma levels of the prostaglandin metabolite 13, 14-dihydro- 15-keto prostaglandin (PGFM) was evaluated in women undergoing elective first-trimester pregnancy termination. Seventy-one women were randomly assigned to either a treatment (n = 45) or control (n = 26) group. Cervical dilatation measured at the time of insertion of the laminaria was 3.0 +/- 0.1 mm compared to 10.2 +/- 0.2 mm at the time of removal of the laminaria 14 to 16 hours later (p less than 0.001). Peripheral levels of PGFM rose from 28.3 +/- 2.4 pg/ml (mean +/- SEM) to 43.0 +/0 2.6 pg/ml at the time of removal of the laminaria (p less than 0.001). Peripheral concentrations of PGFM in controls remained unchanged. Peripheral concentrations of PGFM did not correlate with the patient's symptoms. Although the hydrophilic property of laminaria is considered to be the principal mechanism promoting cervical dilatation, laminaria may alter the elaboration, release, or degradation of uterine prostaglandin F2 alpha. Thus, biochemical as well as mechanical factors may enhance cervical dilatation in laminaria-treated women.

The resumption of cyclic uterine bleeding reportedly accompanies the use of human prolactin (HPRL)-suppressing agents in postpill galactorrhea-amenorrhea. In this laboratory, HPRL suppression with L-dopa was variable and short lived. Basal plasma HPRL levels were elevated before and after as much as five months of therapy. Galactorrhea persisted and mean gonadotropin concentrations were subnormal. An immediate and sustained attenuation of HPRL secretion ( less than 200 per cent) followed the use of 2-Br-alpha-ergocryptine (CB-154). Cyclic gonadotropin secretion resumed and was accompanied by ovulation and, in one instance, pregnancy. The cessation of galactorrhea was positively correlated with the rise in the daily concentration of 17 beta-estradiol. Cyclic postovulatory menstruation continued after the cessation of CB-154 treatment. HPRL levels remained normal. The daily patterns of human follicle-stimulating hormone (HFSH) and human tuteinizing hormone (HLH) secretion created by the suppression of HPRL displayed an inherent rhythmicity identical to that observed at the time of menarche. The inhibitory effects of HPRL appeared directed at cyclic rather than tonic gonadotropin secretion. At the same time, diminished ovarian estrogen production seemed to increase mammary gland sensitivity to HPRL, leading to lactation. One may postulate, therefore, that the ingestion of sex steroids is associated with an over-all suppression of endogenous cyclic and, to a lesser extent, tonic gonadotropin secretion secondary to which ovarian function is attenuated. Without physiologic concentration of circulating estrogen, HPRL induces mammary alveolar function with the production of a milklike secretion.

Banked human milk has been widely used, although its composition and nutritional adequacy for preterm infants are uncertain. We randomized 76 healthy infants of less than or equal to 1500 gm birth weight to ad lib feedings of frozen BHM or a protein-mineral-calorie-enriched formula (Similac Special Care) designed to sustain intrauterine accretion rates; BHM contained 2.2 gm fat/100 ml and 60 kcal/100 ml (gross energy). Infants fed BHM ingested more milk (197 vs 165 ml/kg/day) but less gross energy (118 vs 143 kcal/kg/day); grew less rapidly in weight (15 vs 30 gm/day), length (0.7 vs 1.1 cm/wk), and head circumference (0.8 vs 1.2 cm/wk); and were discharged at a lower weight (2200 vs 2348 gm) and older age (61 vs 47 day) than infants fed formula (P less than 0.02). At 37 weeks' postmenstrual age, infants fed BHM were less responsive to Brazelton inanimate stimuli (mean total score 5.0 vs 7.5; P less than 0.02). With few exceptions, blood amino acids, pH, and serum electrolyte values were similar in both groups. The different caloric intake of our feeding groups may explain only part of the large difference in growth rate. Donor milk should not be fed to preterm infants unless it has been analyzed and the feedings shown to provide a nutrient intake considered appropriate to the needs of these infants.