Maternal corticosteroid and tocolytic treatment and morbidity and mortality in very low birth weight infants.
Explore the source record for details and available documents.
Adrenal Cortex Hormones↗
Biomedical subjects
K G Nelson
Publications and source records attributed to K G Nelson.
Predicting low Apgar scores of infants weighing less than 1000 grams: the effect of corticosteroids.
OBJECTIVE: To evaluate maternal and neonatal factors that predict low Apgar scores in newborns weighing less than 1000 g. METHODS: From a data set of all live-born infants who were delivered between 1979-1991 and who weighed 1000 g or less, we reviewed the records of 837 neonates born at 24-28 weeks' gestation. Potential risk factors were evaluated for associations with a 1-minute Apgar score of 3 or less and a 5-minute Apgar score of 6 or less. Analyses used chi 2 test and multiple logistic regression. RESULTS: The prevalence of 1-minute Apgar scores of 3 or less decreased from 65.9% at 24 weeks to 38.2% at 28 weeks, and the prevalence of 5-minute Apgar scores of 6 or less decreased from 83.3% at 24 weeks to 51.2% at 28 weeks. As the birth weight increased from 500-599 g to 900-1000 g, 1-minute Apgar scores of 3 or less decreased from 77.0% to 39.6%, and 5-minute Apgar scores of 6 or less decreased from 89.2% to 56.4%. Aside from gestational age and birth weight, corticosteroid use was the strongest predictor of Apgar scores above 3 at 1 minute and above 6 at 5 minutes. Male and nonvertex-presenting infants had an increased likelihood of low Apgar scores, as did infants with cord blood pH less than 7.05 or bicarbonate value less than 17 mEq/L. CONCLUSION: Neonates at very low gestational ages and birth weights are more likely than larger or more mature infants to have low Apgar scores. Males, nonvertex-presenting infants, and those who are acidotic at birth also have an increased prevalence of low scores. Infants born to mothers treated with antenatal corticosteroids are less likely to have low Apgar scores. This finding indicates that antenatal corticosteroids may benefit the newborn at birth, before respiratory distress syndrome becomes apparent.
Adrenal Cortex Hormones↗
The effect of cigarette smoking on neonatal anthropometric measurements.
OBJECTIVE: To estimate the effect of maternal cigarette smoking on birth weight, crown-heel length, and ten other neonatal anthropometric measurements. METHODS: Data are from a cohort study on risk factors for fetal growth retardation (FGR) in multiparous women conducted from December 1985 through October 1988. Information on smoking status was collected four times during pregnancy. Data analysis included 1205 singleton infants of women delivering at term. Neonatal anthropometric measurements were obtained within 48 hours of birth, including birth weight, crown-heel length, ponderal index, head and abdominal circumferences, arm length and circumference, femur length and thigh circumference, and triceps, thigh, and subscapular skinfold measurements. Analysis of covariance models were used to assess the independent effect of smoking on each neonatal measurement. RESULTS: Neonates born to women who reported smoking during the first trimester had a 0.6-1.9% reduction in most neonatal anthropometric measurements, resulting in an overall reduction of birth weight of 130 g (4%). Neonates born to women who continued to smoke throughout pregnancy had an average adjusted reduction in birth weight of 189 g (5.9%), compared with a 55 g (1.7%) reduction for neonates born to women who stopped smoking after the first trimester. For women who continued to smoke throughout pregnancy, an increased number of cigarettes smoked was associated with increased reductions in birth weight and neonatal chest and abdominal circumferences. For women who stopped smoking after the first trimester, stopping was a better predictor of neonatal anthropometric measurements than the number of cigarettes smoked early in pregnancy. CONCLUSIONS: Except for the ponderal index, all neonatal anthropometric measurements studied showed some negative effect of maternal cigarette smoking. Head circumference is the measurement least reduced. Smoking cessation is a better predictor of infant size than the number of cigarettes smoked in the first trimester.
Adult↗
The origin and outcome of preterm twin pregnancies.
OBJECTIVE: To define the etiology of preterm twin births and determine the contribution of twin births to preterm birth and related morbidity and mortality. METHODS: The March of Dimes Multicenter Prematurity and Prevention Study included a total of 33,873 women who delivered between 1982-1986, 432 (1.3%) of which delivered twins. Women were classified by reason for preterm birth and ethnicity. Neonates were classified as to stillbirth, neonatal death, and various short-term morbidities. A second data set from one center consisted of infants who weighed 1000 g or less, were born between 1979-1991, and survived to 1 year of age (n = 386, 15% twins); this was used to determine if twins and singletons born at comparable gestational ages have a similar risk for major developmental handicaps. RESULTS: Of the deliveries in the data set, 54% of twins were preterm compared with 9.6% among singletons. Of those born preterm, twins were born at a significantly earlier gestational age than were singletons. Only 2.6% of all neonates born were twins, but they represented 12.2% of all preterm infants, 15.4% of all neonatal deaths, and 9.5% of all fetal deaths. Spontaneous labor accounted for 54% of twin births, premature rupture of membranes accounted for 22%, and indicated deliveries accounted for 23%. Of the indicated preterm births in twins, 44% were due to maternal hypertension, 33% to fetal distress or fetal growth restriction, 9% to placental abruption, and 7% to fetal death. Comparing infants of similar gestational age, twins weighed less, but had a mortality equivalent to that of singletons after 29 weeks. Between 26-28 weeks' gestation, the risk of mortality for twins versus singletons was 1.6 (95% confidence interval 1.1-2.5). Preterm twins did not have significantly more respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, or other short-term morbidity than did preterm singletons. Twins who weighed 500-1000 g and survived to 1 year had a 25% rate of major developmental handicaps. However, when gestational age was controlled, the rate of major handicaps was not higher in twins than in singletons. CONCLUSIONS: Twins accounted for a disproportional amount of preterm birth and associated morbidity and mortality. Also, when preterm twins were compared with preterm singletons and corrected for their gestational ages, the rates of morbidity were similar. Preterm twins weighing less than 1000 g did not have an increased prevalence of major handicaps at 1 year of age compared with preterm singletons.
Birth Weight↗
Comparison of perceived and actual rates of survival and freedom from handicap in premature infants.
OBJECTIVE: Our goal was to learn whether physicians delivering obstetric care accurately estimated rates of survival and freedom from handicap in premature infants. STUDY DESIGN: We surveyed by mail 409 obstetricians and general and family physicians reported to perform deliveries in Alabama to identify their perceptions regarding survival and handicap-free rates of infants born at gestational ages between 23 and 36 weeks, inclusive. Responses were compared with published national rates of survival and freedom from handicap by means of unpaired t tests. RESULTS: A total of 224 physicians responded (55%), and 183 were still practicing obstetrics. They significantly underestimated survival rates from 23 through 34 weeks' gestation (p < 0.05) and freedom from serious handicap from 23 through 36 weeks' gestation (p < 0.05). They advocated early treatment of preterm labor, but < 50% would perform cesarean delivery for fetal distress before 26 weeks' gestation. CONCLUSION: We conclude that physicians delivering obstetric care significantly underestimate survival and freedom from handicap in preterm infants. Perinatal care may be adversely affected by these misperceptions.
Persons with Disabilities↗
Transforming growth factors beta 1, beta 2, and beta 3 messenger RNA and protein expression in mouse uterus and vagina during estrogen-induced growth: a comparison to other estrogen-regulated genes.
Increasing evidence suggests that the differential regulation of multiple peptide growth factors by steroid hormones contributes significantly to the pleiotropic effects elicited in target tissues. We report here an evaluation of the effects of the potent estrogen, diethylstilbestrol, on the expression of the three mammalian transforming growth factor beta (TGF beta) isoforms, TGF beta 1, TGF beta 2, and TGF beta 3, in both the uterus and the vagina of the prepubescent mouse. Immunohistochemical protein detection, in situ hybridization, and Northern RNA analyses demonstrate overlapping but distinct time-dependent and site-specific induction of all three TGF beta genes in the reproductive tract in response to estrogen. Temporal analysis of steady-state levels of the TGF beta mRNAs in the uterus by Northern blotting clearly demonstrates that diethylstilbestrol significantly but transiently up-regulates TGF beta 3 mRNA within 30 min and TGF beta 1 and TGF beta 2 mRNAs by 3 h with decreases to/or below control levels by 6 h. The vagina also responds to diethylstilbestrol with similar kinetics of induction for TGF beta 2 and TGF beta 3 mRNAs as that observed in the uterus; however, TGF beta 1 mRNA levels increase gradually and peak around 16 h after treatment. Investigation of the steroid specificity demonstrates predominant estrogen specificity in the control of TGF beta expression in the immature mouse reproductive tract. In situ hybridization localizes the mRNAs for all three TGF beta isoforms, primarily to the uterine and vaginal epithelium. Unlike the transient nature of TGF beta mRNA induction elicited by estrogen, immunohistochemistry demonstrates that estrogen treatment results in a more prolonged elevation of the proteins for TGF beta 1, TGF beta 2, and TGF beta 3 in the epithelium of both tissues. Investigation of specific binding of 125I-TGF beta 1 by affinity labeling reveals the existence of the receptor/binding proteins (types I, II, and III) in the uterus. Estrogen treatment significantly reduces binding to each of these components in the uterus, which suggests that estrogen may modulate TGF beta responsiveness at the receptor level. A comparison of TGF beta mRNA expression to the induction of other estrogen-regulated genes, TGF alpha, insulin-like growth factor-1, c-myc, progesterone receptor and lactotransferrin reveals that, in general, the TGF beta transcript levels are regulated in a more transient manner by estrogen.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Expression of epidermal growth factor in suprabasal cells of stratified squamous epithelia: implications for a role in differentiation.
There is a disparity in the fact that epidermal growth factor (EGF) can stimulate proliferation of a wide variety of cells in vitro, yet sites of synthesis for this polypeptide in vivo are generally associated with nonproliferative or differentiated cell populations. Unlike other known mitogenic members of the EGF family of ligands, EGF derives from a large (M(r) approximately 130,000) protein that contains multiple EGF-like domains; some of these domains contain putative Ca(2+)-binding sites. In the present study, the mouse vaginal epithelium was used as a prototype tissue to investigate expression of the EGF precursor by stratified squamous epithelia. Stratification and cornification in this tissue are estrogen dependent. In the fully differentiated epithelium, EGF precursor transcripts were detected by in situ hybridization in suprabasal cells; labeling was not observed in the proliferative basal cell compartment. Amplified transcripts of predicted size were detected in the vaginal organ by the reverse transcription-polymerase chain reaction and Northern hybridization of polyadenylated RNA. Antisera to mature EGF or to the COOH-terminal (cytoplasmic) domain of the precursor localized reactivity exclusively to cells of the granular layer. The staining with the precursor antiserum was localized along cell borders, which supports that this protein is translocated to the cell membrane following synthesis, a known property for precursors of EGF-like ligands. EGF expression was not apparent in the atrophic vaginal epithelium of castrates, which did not present a granular layer. Other stratified squamous epithelia in organs such as skin, esophagus, and tongue also revealed EGF/EGF precursor immunoreactivity in the granular layer.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Exposure to diethylstilbestrol during a critical developmental period of the mouse reproductive tract leads to persistent induction of two estrogen-regulated genes.
Exposure to estrogens during critical periods of development induces teratogenic and carcinogenic lesions in the reproductive tracts of humans and experimental animals. It is important to determine the molecular and cellular targets of estrogenic chemicals and to establish the mechanisms by which interactions of estrogens with the developing genital tract results in permanent lesions of growth and differentiation. The experiments presented here were designed to examined the effects of neonatal estrogen exposure on the expression of two genes, lactoferrin and epidermal growth factor, that are subject to steroid hormone regulation. Using in situ and Northern RNA hybridization, immunoblotting, and immunohistochemistry, our data demonstrate that exposure to the synthetic estrogen, diethylstilbestrol, during a critical neonatal period results in the persistent ovary-independent induction of mRNA and protein encoded by these two genes in the mouse uterus and vagina. The constitutive expression of lactoferrin and EGF, and probably other estrogen-regulated genes, may contribute to the establishment of a permanently "estrogenized" phenotype which is then instrumental in the development of abnormal tissue morphogenesis, function, and neoplasia in the rodent reproductive tract.
Animals↗
Coupling of dual signaling pathways: epidermal growth factor action involves the estrogen receptor.
Epidermal growth factor (EGF) reproduces many of the effects of estrogen on the murine female reproductive tract and may partially mediate estrogen-induced growth and differentiation. This study was performed to investigate the mechanism by which EGF elicits estrogen-like actions in the whole animal. EGF was administered to adult ovariectomized mice by slow release pellets implanted under the kidney capsule. The induction of uterine DNA synthesis and phosphatidylinositol lipid turnover by EGF or administration of diethylstilbestrol (5 micrograms/kg), a potent estrogen, was attenuated by the estrogen receptor antagonist ICI 164,384. Furthermore, EGF mimicked the effects of estrogen on enhanced nuclear localization of the estrogen receptor and the formation of a unique form of the estrogen receptor found exclusively in the nucleus. These results suggest that EGF may induce effects similar to those of estrogen in the mouse uterus by an interaction between the EGF signaling pathway and the classical estrogen receptor. The demonstration of cross-talk between polypeptide growth factors and steroid hormone receptors may be of importance to our understanding of the regulation of normal growth and differentiation as well as the mechanisms of transmission of extracellular mitogen signals to the nucleus.
Animals↗
Lactoferrin expression in the mouse reproductive tract during the natural estrous cycle: correlation with circulating estradiol and progesterone.
Lactoferrin (LTF), an iron-binding glycoprotein present in most exocrine secretions and in the secondary granules of polymorphonuclear leucocytes (PMN), is regulated by estrogen in the mouse reproductive tract. We investigated the expression of LTF mRNA and protein during the natural estrous cycle to increase our understanding of how this uterine secretory protein is regulated under physiological conditions. There was a positive correlation between LTF mRNA expression in the genital tract and serum estradiol (E2) concentrations. When E2 peaked in proestrus, LTF mRNA and protein were expressed in the uterus; however, during metestrus, when both E2 and progesterone levels were high, LTF mRNA was expressed, while LTF protein was decreasing. LTF protein expression may be hindered by progesterone or some other local factor in the endometrial epithelium after ovulation. Immunohistochemistry demonstrated two distinct staining patterns for LTF in the vaginal and endometrial epithelium. In one staining pattern, the colorimetric reaction was noted over the cytoplasm, and in the other, the nuclear region stained more intensely. This suggests the possibility that in addition to its known role as a secretory protein, LTF may be transported to the nucleus, serving an autocrine role. Our results also indicated that LTF protein is a useful marker for tracking PMN. Nonproliferating epithelial cells in the vagina and endometrium may synthesize chemotactic and/or adhesion molecules for PMN.
Animals↗
Transforming growth factor-alpha is a potential mediator of estrogen action in the mouse uterus.
To better understand the role of peptide growth factors in sex steroid hormone-mediated growth of the female reproductive tract, the effect of estrogen on the expression of transforming growth factor-alpha (TGF alpha) in mouse uterus was investigated. Our results show that estrogen induces the expression of TGF alpha mRNA in the mouse uterus in a dose- and time-dependent manner. The up-regulation of TGF alpha transcripts occurs predominantly in uterine epithelial cells. RIA and Western blot analysis demonstrate that immunoreactive TGF alpha protein is secreted at high levels into mouse uterine luminal fluid after estrogen treatment. The induction of uterine TGF alpha mRNA is specific to estrogen; nonestrogenic steroids did not induce expression. Antibody specific to TGF alpha significantly reduces estrogen-mediated uterine growth, which supports the concept that TGF alpha is a mitogen for the reproductive tract. Analysis of TGF alpha/EGF receptors by binding, affinity labeling, and phosphorylation studies indicates that functional receptors are present in the mouse uterus after estrogen exposure. Thus, our data support a physiological role for TGF alpha and its receptor pathway in the female mouse reproductive tract.
Animals↗
The influence of previous low birth weight on birth weight, gestational age, and anthropometric measurements in the current pregnancy.
The effect of a previous low birth weight birth (less than 2750 g) was examined using a series of regression analyses. Effects on birth weight were partitioned into those associated with preterm delivery (128 g) and term delivery (178 g). Among term births, a mean difference of 107 g was associated with a previous birth of less than 2750 g, even after controlling for other risk factors including smoking, drug and alcohol use, maternal race, size, and hypertension. The pattern of measurements seen after a previous birth of less than 2750 g included significantly smaller head, chest, abdomen, arm, and thigh circumferences, but an insignificant impact on skinfold thicknesses and no significant effect on length measurements.
Anthropometry↗
Epidermal growth factor replaces estrogen in the stimulation of female genital-tract growth and differentiation.
The in vivo studies presented here demonstrate that epidermal growth factor (EGF) is an important autocrine and/or paracrine mediator of estrogen-induced growth and differentiation in mouse uterus and vagina. An antibody specific for EGF significantly inhibited estrogen-induced uterine and vaginal growth, thereby implicating EGF involvement in estrogen action. Furthermore, EGF administered via slow-release pellets in ovariectomized mice acted as a potent uterine and vaginal mitogen as well as an inducer of vaginal keratinization. Experiments with ovariectomized, adrenalectomized, hypophysectomized mice indicated that EGF mitogenesis does not require pituitary or adrenal hormones. Treatment with EGF also mimicked estrogen in the induction of uterine lactoferrin (a major estrogen-inducible secretory protein) mRNA and protein. These data suggest that EGF has estrogen-like effects in the promotion of cell growth in the reproductive tract and that EGF may serve as an important mediator of estrogen action in vivo.
Adrenalectomy↗
Localization of the estrogen receptor in uterine cells by affinity labeling with [3H]tamoxifen aziridine.
The possibility that estrogen receptors may exist in uterine plasma membranes was investigated by covalent labeling of estrogen receptors in mouse uterine cells with [3H]tamoxifen aziridine (TA). Isolated epithelial and stromal cells of immature mice were incubated with [3H]TA in the presence or absence of unlabeled tamoxifen, homogenized and separated into nuclear, cytosolic and microsomal fractions by differential centrifugation. These fractions were subjected to SDS-polyacrylamide gel electrophoresis and the proteins labeled covalently with TA were visualized by autoradiography. Proteins labeled specifically with [3H]TA were observed almost exclusively in the nuclear fraction of both epithelial and stromal cells. In contrast, very little labeled protein was detected in the cytosolic or microsomal fraction. Although these data do not preclude the possibility that estrogen binding sites are present in plasma membranes of uterine cells, this cellular fraction is definitely not labeled to a significant extent by [3H]TA. Thus, if membrane estrogen binding sites exist, their structural conformations may be different from that of nuclear estrogen receptors.
Affinity Labels↗
Black-white differences in newborn anthropometric measurements.
The mean birth weight of black infants is consistently less than that of white infants. In 1518 low-income multiparous women, the mean difference in singleton births was 171 g, of which 38 g was partitioned to preterm births and another 35 g reflected lower gestational ages in term births. A series of regression analyses were used to determine the effect of black race on various newborn measurements in 1205 term newborns, adjusting for other known risk factors. In this model, black race accounted for a mean decrease of 148 g in weight and 0.52 cm in length. There were also significant decreases in mean head (0.44 cm), chest (0.66 cm), and abdominal (0.56 cm) circumferences. Arm and leg lengths were not different, but black arm circumferences (0.14 cm) were significantly larger. Triceps and thigh skin fold measurements were not statistically different, but black subscapular skin fold values were significantly smaller (0.17 mm). The ponderal index in blacks was significantly less than in whites. These data suggest that in this population, intrinsic and/or extrinsic factors associated with race account for most smaller black newborn measurements and for much of the racial difference in birth weight.
Alabama↗
Epidermal growth factor binding and receptor distribution in the mouse reproductive tract during development.
The ontogeny of the epidermal growth factor (EGF) receptor in the different cell types in the neonatal and immature mouse uterus and vagina was examined. Immunohistochemical examination of prenatal and neonatal reproductive tracts with a polyclonal antibody to the EGF receptor shows immunoreactive EGF receptors as early as Day 13 of gestation. Autoradiographic analysis of tissue sections at 3 to 17 days of age (the day of birth is Day 1) demonstrates that both uterine and vaginal epithelial and stromal cells are capable of binding 125I-labeled EGF. Both the 125I-labeled EGF autoradiography and immunohistochemistry in whole tissue show higher EGF receptor levels in the uterine epithelium than the uterine stroma. The presence of EGF receptors was also confirmed by affinity labeling and Scatchard analysis of isolated uterine cell types at 7 and/or 17 days of age. However, in contrast to the autoradiography and immunohistochemistry data of intact tissue, the affinity labeling and Scatchard data of isolated cells indicate that the uterine stroma contains higher levels of EGF receptor than that of the uterine epithelium. The reason for this discrepancy between the different techniques is, as yet, unknown. Regardless of the differences in the actual numbers of EGF receptors obtained, our data demonstrate that the developing mouse reproductive tract contains immunoreactive EGF receptors that are capable of binding 125I-labeled EGF.
Affinity Labels↗
Mycoplasmal infections of cerebrospinal fluid in newborn infants from a community hospital population.
Mycoplasma hominis or Ureaplasma urealyticum have previously been isolated from cerebrospinal fluid (CSF) in 13 of 100 newborn infants tested from a high risk university hospital population where the mothers were of predominantly lower income and socioeconomic status and had often received little or no prenatal care. We sought to determine whether such infections occur in neonates born to women cared for mainly through private obstetric practices and who delivered in 4 suburban community hospitals. CSF cultures were done in 318 infants during an 8-month period. M. hominis was isolated from 9 and U. urealyticum from 5 CSF cultures. Four infants infected with U. urealyticum and 3 infected with M. hominis were born at term. One infant infected with U. urealyticum had a birth weight of less than 1000 g. In 5 infants clearance of the infecting organism was documented without specific treatment. Twelve infants had good perinatal outcomes regardless of treatment and 2 died. One death in a 2240-g infant infected with M. hominis was associated with Haemophilus influenzae sepsis and pneumonia. The other death occurred 3 days after birth in a 630-g infant infected with U. urealyticum who had evidence of meningitis and intraventricular hemorrhage. Results of this study suggest that mycoplasmas are common causes of neonatal CSF infections, not only in high risk populations, but also in the general population.
Alabama↗
Intrauterine growth retardation: standards for diagnosis.
An intrauterine growth-retarded infant is commonly defined as one weighing less than the 10th percentile in birth weight for its gestational age. However, because there is no standard population from which to derive these percentiles, the birth weights that serve as the cutoff point in various published studies may differ by several hundred grams at any gestational age. For this reason, we examined the studies from which the currently used 10th-percentile standards are derived to determine which factors may be responsible for the variation. In addition to obvious differences in the populations and geographic areas on which they were based, studies differed in how gestational age was determined, whether the gestational age was "rounded" or given in completed weeks, which types of infants were excluded, whether the studies were hospital or population based, and whether they were controlled for sex of the infant and race and parity of the mother. These differences in study methodology may be as or more important than the population differences in defining the 10th percentile cutoffs. A single national standard for intrauterine growth retardation would allow comparison between studies of risk factors, diagnostic tests, management, and long-term follow-up status of fetuses and infants with intrauterine growth retardation.
Birth Weight↗