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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.

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.

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.

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.

Nonpuerperal alactorrhea and amenorrhea have been reported following the use of oral contraceptives. Treatment of this condition with ergot alkaloids has proved to be of great therapeutic value. Pretreatment plasma hLH and hFSH concentrations in 13 women with postqill galactorrhea-amenorrhea (PPGA) were 6.6 plus or minus 0.6 (SE.) and 5.0 plus or minus 0.8 mlU/ml, respectively. The mean prolactin concentration was 80.7 plus or minus 13.2 ng/ml. After complete evaluation in which diagnostic evidence of pituitary tumor was absent, the patients were treated with ergocryptine (CB-154). The mean hPRL concentration at 14 days of therapy was 7.8 p;us or minus 1.9 ng/ml. Cyclic gonadotropin secretion resumed in all but one instance; ovulation was confirmed on the basis of a biphasic temperature chart and in 5 cases, endometrial biopsy. Measurement of serum dopamine-beta-hydroxylase (DBH) activity indicated a significant decline at the end of 8 weeks of CB-154 therapy. The fall in hPRL was not necessarily associated with a fall in DBH. The majority of women in this study exhibited a consistent personality suggesting varying degrees of anxiety unrelated to the PPGA and usually antedating the use of oral contraceptives. PPGA was found in women without hyperprolactinemia, but altered hPRL secretion was evident in all instances. The data suggest that the disorder of cyclic gonadotropin secretion is related to altered hPRL secretion, but the mechanism is possibly related to a catecholamine abnormality. The data support the presence of an inherent cyclic mechanism for the secretion of gonadotropins. CB-154 therapy does not affect conception, and no teratogenic effects were observed in 2 infants born to women who had received CB-154 during the first 40 days of gestation.

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.

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.

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 incidence of symptomatic patent ductus arteriosus (sPDA) in very-low-birth-weight infants has been reported almost exclusively from referral centers. Moreover, the incidence has varied considerably. We prospectively evaluated the incidence and risk factors of sPDA in a totally inborn population of infants less than or equal to 1500 g birth weight (n = 120) receiving conservative fluid management and examined the role of echocardiography in predicting sPDA before clinical signs are evident. The incidence of sPDA was relatively low (16%) and the age at onset was relatively late (mean +/- S.E. = 14.7 +/- 3.0 days) when compared to prior reports. Echocardiographic changes preceded physical and radiographic findings of sPDA. Fluid volume within the range administered to our infants was unrelated to the occurrence of sPDA. However, risk factors identifiable within 24 h of birth were defined: obstetric estimate of gestational age, race, mean fluid volume intake in the initial 24 h, and early treatment with volume expanders. From these risk factors, 79% of infants with sPDA and 79% without sPDA could be predicted by stepwise discriminant function analyses. These findings may be employed in studies needed to assess the benefit of early surgical or pharmacologic therapy for infants at highest risk for sPDA.

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.

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.

Plasma samples obtained throughout the normal menstrual cycles of six women were analyzed for dopamine-beta-hydroxylase activity (DBH), norepinephrine (NE), follicle-stimulating hormone, luteinizing hormone, and prolactin. Neither DBH activity nor NE concentrations paralleled changes in plasma gonadotropins and prolactin. No consistent pattern of either plasma DBH activity or NE concentrations during the normal menstrual cycle was noted. Thus, an association between peripheral sympathetic nervous system activity and the midcycle surge in plasma gonadotropins reported by others was not reproducible in our study of normally menstruating women.

In a further evaluation of the use of oral thyrotropin-releasing hormone (TRH) in puerperally lactating women, a radioimmunoassay for its measurement has been developed. Its concentration in plasma as well as that of prolactin (PRL), thyrotropin (TSH) and thyroxine (T4) were measured following either intravenous or oral administration of TRH. Basal concentrations of TRH in 14 normally cycling women ranged from less than 5 to 17 pg/ml. Two luteal phase studies produced peaks in plasma TRH 5 to 10 minutes after 100 micrograms of TRH administered intravenously with a return to basal concentrations within 2 to 3 hours. In 10 normally menstruating women, ingestion of 10 mg of TRH orally resulted in plasma TRH which peaked at 423 +/- 123 pg/ml (standard error of the mean) at 30-minutes. Plasma PRL, TSH, and T4 also increased and remained slightly elevated at 4 hours. These 8-hour studies were performed in a puerperal lactating woman who had ingested 10 mg of TRH orally twice a day for 7 days prior to blood sampling. TRH concentrations declined throughout each day while TSH rose slightly in the first 1 to 2 hours but remained within normal limits. The prolonged administration of 10 mg of TRH orally twice daily to three puerperally lactating women resulted in elevations in plasma TRH 2 to 3 hours following hormone administration, yet no significant increases in plasma TSH were observed. Both endogenous TRH and TSH were measured before and after 22 nursing events in nine puerperally lactating women. There was no change in the concentration of either substance and all values were similar to those obtained in normally menstruating women.

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.

The causes of puerperal infertility in lactating women are poorly understood. The controlling centres may be either the hypothalamic-pituitary axis or the ovary (or both). We studied the secretory dynamics of prolactin and gonadotropins in healthy, normal, lactating and non-lactating women after administering either gonadoliberin to assess pituitary responsiveness or human menopausal gonadotropins to assess ovarian responsiveness during the puerperium. A reciprocal relationship was observed between the secretion of gonadotropins and the secretion of prolactin after the nipples of mothers who were breast-feeding had been stimulated for 30 min. The absence of a short-loop negative feedback control by prolactin for gonadotropin secretion was not confirmed because cyclic secretion of gonadotropin was not necessarily impaired by hyperprolactinaemia. Hyperprolactinaemia did, however, appear to impair the function of the corpus luteum in women suffering from non-puerperal galactorrhoea. We postulate a multifactorial mechanism for puerperal infertility based initially on the peripheral concentration of prolactin and gonadotropins and, in some poorly defined way, on the cerebral concentration of catecholamines.

Concentrations of human chorionic gonadotropin (HCG), human placental lactogen (HPL), prolactin (PRL), follicle-stimulating hormone (FSH), estradiol (E2) and progesterone (P) were measured in serum and fluid from ovarian theca lutein cysts (TC) in patients with gestational trophoblastic disease (GTD). Either intact hydatidiform mole (HM) or persistent GTD was present. The values were compared to serum hormone concentrations in ten GTD patients whose ovaries were not enlarged. In the presence of intact HM and TC, significant elevations in the mean serum concentration of HCG, PRL, P and E2 were observed when compared to levels in GTD patients with normal-sized ovaries (P less than .01). Serum FSH and HPL were not elevated in either control or TC patients. The mean concentration of P in cyst fluid from patients with intact HM was higher than that in patients with persistent GTD (P less than .05). From both groups of GTD patients with TC, the mean concentrations of P in cyst fluid were higher than those in the sera. These findings suggest that besides the markedly elevated HCG levels generally seen in TC patients, other hormones, such as P, PRL and E2 are elevated and may be involved in the formation and/or maintenance of TC.

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.

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.

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.

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.

Regulation of prolactin secretion was investigated by perfusing rat pituitaries in vitro. Two pituitary glands from inbred rats were transplanted beneath the renal capsule of a third recipient rat. Three weeks later, the transplanted kidney was removed and perfused in vitro with a defined cell-free medium. Normal renal function was maintained during perfusion, and cell morphology of the transplants remained unchanged as assessed by electron microscopy. Pituitary prolactin content did not change after 120 min of perfusion despite release of approximately 10 micrograms of hormone. Thyrotropin-releasing hormone (10 ng/ml) did not stimulate prolactin release; dopamine (20 ng/ml) rapidly, but transiently inhibited prolactin release; bromocriptine (20 ng/ml) rapidly and persistently inhibited prolactin release; haloperidol (100 ng/ml) blocked the inhibition by dopamine or bromocriptine, but when given alone inhibited prolactin release. Finally, prolactin release was also inhibited by the presence of 100 and 200 ng/ml, but not 50 ng/ml of NIAMDD RP-1 rat prolactin. It is concluded that in vitro perfusion of transplanted rat pituitaries provides a new model for studying the direct effect of agents on the secretion of prolactin from the pituitary and that rat prolactin and/or its metabolites directly inhibit pituitary prolactin secretion.

Further substantiation of the interaction between psychological disease and the onset of galactorrhea-amenorrhea is presented in women who underwent intensive psychometric and neuroendocrine evaluation prior to the use of the dopamine against 2-Br-alpha-ergocryptine (CB-154). Normalization of a previously distorted psychometric test profile in each woman was accompanied by a profound decline in prolactin and an unexpected alteration in the peripheral concentrations of norepinephrine and dopamine-beta-hydroxylase. Cesation of galactorrhea and resumption of menses were observed in each instance.

Although photon absorptiometry is increasingly used to evaluate bone mineral content of neonates, its reliability in this age group is unclear. The midradius or middistal radius of 12 growing preterm infants was scanned, using a Norland 278 Densitometer. Proper examiner technique and densitometer calibration were first verified. In three infants, the bone edges were not consistently discernible from soft tissue. In the remaining nine infants, apparatus variability (the percent change in bone mineral content of scans repeated without repositioning the infant) was comparable to intraexaminer and interexaminer variability (determined after the same or a different examiner repositioned the infant and repeated the scan). The variability for successive scans ranged from -73% to +60% (SD, 5% to 36%). Adequate reliability for preterm infants remains to be documented for commercially available photon absorptiometers by in vivo studies.

Stimulation and inhibition tests are proposed for evaluating prolactin secretion. Thyrotropin-releasing hormone (TRH) stimulates the release of prolactin from the pituitary. Chlorpromazine acts presumably at the hypothalamic level to increase prolactin secretion. L-Dopa (D,L-alpha-hydrazino-alpha-methyl-beta-[3,4-di-hydroxyphenyl]) has the opposite effect; it inhibits prolactin secretion and may be effective in suppressing galactorrhea.