David C. Heilbron

Neonatal morbidity according to gestational age and birth weight from five tertiary care centers in the United States, 1983 through 1986.

OBJECTIVES This study details the incidence, by gestational age and birth weight, of specific neonatal morbidities in singleton neonates without major congenital anomalies. STUDY DESIGN Data were prospectively collected on all deliveries at five tertiary centers in the United States during the years 1983 through 1986. Pregnancies were meticulously dated and the gestational ages of the neonates at delivery were confirmed by Dubowitz score. RESULTS The incidence of respiratory distress syndrome gradually decreases with increasing gestational age until 36 weeks. A marked decrease in the incidence of necrotizing enterocolitis, patent ductus arteriosus, intraventricular hemorrhage, and sepsis occurs after 32 completed weeks. The number of days of mechanical ventilation for respiratory distress syndrome and newborn stay in the tertiary care facility also were significantly reduced after 32 weeks. CONCLUSIONS The incidence of both respiratory distress syndrome and patent ductus arteriosus is markedly decreased by both increasing gestational age and birth weight. The incidence of grade III and IV intraventricular hemorrhage, necrotizing enterocolitis, and sepsis virtually vanishes after 34 weeks. These data relating neonatal morbidities to gestational age are important to the obstetrician in the critical decision regarding the timing of delivery and to the parents, who can benefit from a realistic prediction of the neonatal course.

Genetic analysis of a polymorphism in the human apoA-V gene effect on plasma lipids

Recent discovery and characterization of APOAV suggests a role in metabolism of triglyceride (TG)-rich lipoproteins. Previously, variation at the APOAV locus was shown to modestly influence plasma TGs in normolipidemic samples. The aims of this study were to assess the effects of a polymorphism in APOAV (T-1131C) in terms of its frequency among three dyslipidemic populations and a control population, differences of allele frequency across available ethnic groups, and associations with specific lipoprotein TG and cholesterol compartments. We found a striking elevation in the frequency of the rare allele in a Chinese population (P = 0.0002) compared with Hispanic and European populations. The rare allele of the polymorphism was associated with elevated plasma TG (P = 0.012), VLDL cholesterol (P = 0.0007), and VLDL TG (P = 0.012), LDL TG (P = 0.003), and HDL TG (P = 0.016). Linear regression models predict that possession of the rare allele elevates plasma TG by 21 mg/dl (P = 0.009) and VLDL cholesterol by 8 mg/dl (P = 0.0001), and reduces HDL cholesterol by 2 mg/dl (P = 0.017). The association of the polymorphism with altered lipoprotein profiles was observed in combined hyperlipidemia, hypoalphalipoproteinemia, and hyperalphalipoproteinemia, and in controls. These findings indicate that APOAV is an important determinant of plasma TG and lipoprotein cholesterol, and is potentially a risk factor for cardiovascular disease.

Expressing glomerular filtration rate in children

We have reviewed the studies that provide the current standards of reference for glomerular filtration rate (GFR) in normal children from 14 days to 12 years of postnatal age. These standards currently are presented as ml/min per 1.73 m2, i.e., adjusted to average adult body surface area. Children from birth to 1 year of age have adjusted values below the adult range, making comparisons of observed to reference values difficult. Currently, there is no accepted way of obtaining reference values that vary smoothly with age. An analysis of the absolute GFR values in normal children taken from published studies led to an equation that estimates average GFR in relation to weight and term-adjusted age from-2 months (7 months gestational age) to 12 years in children at least 14 days post delivery. When these data are transformed to percentage of normal (% nl) for age and weight (i.e., percentage of the estimated average), it is possible to describe approximate apparent lower limits of normal GFR as is now done for adults and older children. For children with loss of renal mass, GFR expressed as % nl for age and weight provides a convenient standardization which has several useful applications. First, results expressed as % nl for children of different ages, particularly under 1 year of age, can be combined with those of older children for summary purposes. Second, the course of GFR measured serially in children is more appropriately described using this method for expressing GFR. Reporting GFR in absolute values is also useful, particularly in patients whose body mass is significantly distorted or whose absolute GFR is low.

Noninvasive assessment of cardiomyopathy in normotensive diabetic patients between 20 and 50 years old

PURPOSE To further the understanding of diabetic heart disease, we tested the hypothesis that an asymptomatic group of normotensive diabetic patients between 20 and 50 years old had a restrictive cardiomyopathy independent of clinically significant coronary artery disease. PATIENTS AND METHODS Quantitative two-dimensional echocardiography and stress myocardial perfusion scintigraphy were performed to detect and characterize the cardiac abnormalities in this study group comprising 88 patients with rigorously classified diabetes and 65 volunteer control subjects. RESULTS Diabetic patients were shown to have a mildly reduced left ventricular end-diastolic volume index: 50.1 +/- 8.2 and 52.1 +/- 14.7 mL/m2 for patients with type I and type II diabetes, respectively, versus 58.9 +/- 11.7 mL/m2 for control subjects. The left ventricular diastolic filling was also impaired in diabetic patients as reflected by a lower atrial emptying index: 0.73 +/- 0.24 and 0.76 +/- 0.3 for type I and type II diabetics, respectively, compared with 1.14 +/- 0.24 for control subjects. Exercise tolerance was normal in subjects with type I diabetes and slightly reduced in subjects with type II diabetes. Only one patient developed regional ischemia on thallium exercise testing. CONCLUSION Using a comprehensive, noninvasive approach, we have shown that asymptomatic normotensive patients with type I or type II diabetes who were between 20 and 50 years old had a restrictive cardiomyopathy characterized by mildly reduced left ventricular end-diastolic volume and altered left ventricular compliance independent of critical coronary artery disease.

Increased depth of trophoblast invasion after chronic constriction of the lower aorta in rhesus monkeys

OBJECTIVE Our purpose was to investigate whether a reduction in uteroplacental perfusion pressure would produce changes in trophoblast-uterine interactions at the cellular level. STUDY DESIGN Strictures were placed around the abdominal aortas of rhesus monkeys at 116 +/- 7 days of pregnancy to reduce uteroplacental perfusion pressure. Placental bed biopsy specimens were obtained at cesarean section, and cytotrophoblasts were identified by means of an anticytokeratin antibody. RESULTS In monkeys without aortic strictures, interstitial trophoblast invasion was restricted to the outer half of the endometrium. Endovascular trophoblast invasion involved the entire endometrial portion of uterine vessels and extended through the subjacent half of their myometrial segments. In seven of nine monkeys with aortic strictures the depth of interstitial trophoblast invasion was substantially increased and extended throughout the entire decidua and at least a portion of the myometrium. In contrast, the pattern of endovascular trophoblast invasion was identical to that observed in the placental beds of control animals. CONCLUSION These results suggest that uteroplacental perfusion pressure or oxygen content may be important physiologic factors controlling the depth of interstitial cytotrophoblast invasion.

Clinical Differences Among Women with and Without Self-Reported Perimenstrual Asthma

BACKGROUND Studies suggesting that 30% to 40% of asthmatic women report significant perimenstrual (late luteal phase) exacerbations of asthma are primarily retrospective, rely on subjective findings and do not demonstrate a consistent association between asthma and the menstrual cycle. OBJECTIVE In this exploratory analysis, women with and without self-reported perimenstrual exacerbations of asthma (PMA) were examined prospectively to determine the association between asthma and the menstrual cycle and to characterize associated clinical factors. METHODS Thirty-two adult asthmatic women with regular menstrual periods recorded daily asthma symptoms, medication use, and peak expiratory flow rate (PEFR) over six consecutive menstrual cycles, and underwent spirometry and methacholine bronchoprovocation during the luteal and follicular phases of 2 cycles. RESULTS Nine of 32 subjects (28.2%) reported PMA. Daily means of rescue medication use and AM peak flow computed for each perimenstrual day demonstrated significant non-parallelism of group profiles; subjects with PMA had increasing inhaled short acting beta 2-agonist use and decreasing AM peak flow rates during the perimenstrual interval. Luteal-follicular phase differences in FEV1 or methacholine bronchoprovocation between the groups were not detected. Subjects with PMA were older (P=.007), had longer duration of asthma (P=.039), and increased baseline asthma severity (P=.076) compared with subjects without PMA. CONCLUSION The findings of this study suggest that women with self-reported perimenstrual asthma demonstrate perimenstrual differences in rescue bronchodilator use and AM peak flow and appear to constitute a distinct subset of women with asthma who are older, have longer duration of asthma, and increased severity of asthma compared with women without self-reported perimenstrual asthma. These factors identify women who require close monitoring of their asthma during their menstrual cycles.

A comparison of methods for quantitating fetal heart rate variability

Fetal heart rate (FHR) variability is thought to be an important index of fetal health. In the presence of normal variability, the fetus is vigorous, but lack of beat-to-beat variability may be associated with fetal compromise. A distinction between short-term variability (STV) (beat-to-beat changes between successive beats) and long-term variability (LTV) (rhythmic fluctuations in FHR) has not been made to date. We have utilized computer programs to compare three pairs of mathematical indices and one visual index of FHR variability. Among the three pairs of indices designed for detection of STV and LTV, de Haans short-term and long-term indices exhibited the least interdependence, and the long-term index was completely insensitive to artifically generated pure STV. Yehs short-term and long-term indices exhibited substantial positive interdependence. Hons visual index appears to detect LTV primarily rather than STV. When the effect of progression of labor on FHR variability was examined, no conclusions were possible because of inconsistencies between patients. Ultimately, the clinical value of any one of these indices awaits testing of their ability to define fetal well-being or fetal distress.

Growth factor activity in the blood of women in whom preeclampsia develops is elevated from early pregnancy

Preeclampsia is a pregnancy-specific disorder of uncertain cause and pathophysiology that appears to be associated with endothelial cell injury. Our current studies demonstrate that a pregnancy growth factor activity is elevated compared with postpartum values in the blood of women with preeclampsia months before the onset of clinical manifestations of toxemia. A cohort of primigravid women was followed throughout pregnancy and multiple serial plasma samples from six women with preeclampsia and six matched normal women were assayed for mitogenic activity. The data indicated that the ratio of predelivery/postdelivery plasma mitogenic activity was greater in women predestined to meet strict criteria for the diagnosis of preeclampsia compared with matched normal primigravid women. Growth factor activity could distinguish women in whom preeclampsia would develop from their normal peers throughout pregnancy, and as early as the first trimester of gestation (p less than 0.05). Similar studies performed with plasma obtained greater than 6 weeks post partum, when the two groups of patients were clinically indistinguishable, revealed no differences in this index of mitogenic activity. Our results indicate that elevated mitogenic activity ratios of prepartum versus postpartum plasma antedate the clinical recognition of preeclampsia, and return to normal with the resolution of the syndrome.

Patterns of urinary enzyme excretion in healthy subjects

Abstract The urinary excretion of leucine aminopeptidase, arylsulphatase, β-glucuronidase, lactate dehydrogenase, alkaline and acid phosphatase was studied for ten 12th periods in 8 subjects. After reducing the methodological error by using gel filtration to remove interfering substances from urine, biological patterns of enzyme excretion could be recognized. Both the central level and dispersion of results characterize each subject. No consistent circadian fluctuation was demonstrable. Results expressed either as enzyme activity/urinary volume, or excreted urinary enzyme activity/12 h, or urinary enzyme activity/mg of creatinine all conformed to logarithmically normal distributions, allowing analysis of variance to estimate the significant contributions of intra- and inter-individual differences to total variability. Variability of enzyme excretion was least when results were related to creatinine excretion, rather than to urinary volume or time. The model presented should improve recognition of pathological enzyme excretion.

Survey of men and women residents entering United States obstetrics and gynecology programs in 1981

In July 1981, questionnaires were distributed to 1,128 residents entering the field of obstetrics and gynecology throughout the United States; 546 (48%) were returned and evaluated, 229 from women (42%) and 317 from men (58%). Factors that related to the choice of the specialty showed a universal interest in the birthing process and the surgical aspects of the specialty, with a large majority also interested in health education, endocrinology, primary care of young people, and achievement of a greater understanding of sexuality. Private partnership practice was favored by most of the respondents. Men attributed a greater importance to income than did women, who were more interested in a salaried practice and less irregularity of hours. Women tended to be more liberal on questions that were related to controversial medical and ethical issues in the field of obstetrics and gynecology. Role models, half of whom were teachers, were equally common to men and women (66%).