Charles R. Rosenfeld

The neonatal blood count in health and disease.I. Reference values for neutrophilic cells

Reference ranges for absolute total neutrophils/mm3, absolute immature neutrophils/mm3, and the fraction of immature to total neutrophils (I:T proportion) during the first 28 days of life are developed from 585 peripheral blood counts obtained from 304 normal neonates and 320 counts obtained from 130 neonates with perinatal complications demonstrated to have no statistically significant effect on neutrophil dynamics. Perinatal factors other than bacterial disease which significantly alter neutrophil dynamics include maternal hypertension, maternal fever prior to delivery, hemolytic disease, and periventricular hemorrhage. The predictive value of these reference ranges in identifying bacterial disease in the first week of age varies with the neutrophil factor evaluated and the clinical setting. Neutropenia in the presence of respiratory distress in the first 72 hours had an 84% likelihood of signifying bacterial disease, whereas neutropenia in the presence of asphyxia had a 68% likelihood of signifying bacterial disease. An abnormal I:T proportion had an accuracy of 82% and 61%, respectively, in the same clinical settings. Elevations of either immature or total neutrophils were less specific. Interpretation of abnormal neutrophil factors must include consideration of both infectious and noninfectious perinatal events.

Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less.

OBJECTIVE. Ductus arteriosus (DA) closure occurs within 96 hours in >95% of neonates >1500 g in birth weight (BW). The prevalence and postnatal age of spontaneous ductal closure in neonates ≤1000 g in BW (extremely low birth weight [ELBW] neonates) remain unclear, as does the incidence of failure to close with indomethacin. Therefore, we prospectively examined the prevalence, postnatal age, and clinical variables associated with spontaneous DA closure, occurrence of persistent patent DA, and indomethacin failure in ELBW neonates. METHODS. Neonates delivered at Parkland Memorial Hospital from February 2001 through December 2003 were studied. Those with congenital heart defects or death <10 days postnatally were excluded. Echocardiograms were performed 48 to 72 hours postnatal and every 48 hours until 10 days postnatally. RESULTS. We studied 122 neonates with BW of 794 ± 118 (SD) g and estimated gestational age (EGA) of 26 ± 2 weeks. Spontaneous permanent DA closure occurred in 42 (34%) neonates at 4.3 ± 2 days postnatally, with 100% closure by 8 days. These neonates were more mature, less likely to have received antenatal steroids or have hyaline membrane disease (HMD; 52% vs 79%), and more likely to be growth restricted (31% vs 5%) and delivered of hypertensive women. Using regression analysis, EGA and absence of antenatal steroids and HMD predicted ductal closure. Ten (8%) neonates with early DA closure reopened and required medical/surgical closure. Eighty neonates had persistent patent DA; 7 were surgically ligated, and 5 remained asymptomatic, with 4 of 5 closing after 10 days postnatally. Sixty-eight (85%) received indomethacin at 6.2 ± 4 days postnatally; 41% failed therapy and had no distinguishing characteristics. CONCLUSIONS. Spontaneous permanent DA closure occurs in >34% of ELBW neonates and is predicted by variables related to maturation, for example, EGA and an absence of HMD, whereas indomethacin failure could not be predicated.

A prospective comparison of selective and universal electronic fetal monitoring in 34,995 pregnancies

Abstract We investigated the effects of using intrapartum electronic fetal monitoring in all pregnancies, as compared with using it only in cases in which the fetus is judged to be at high risk. Pr...

Nitric oxide contributes to estrogen-induced vasodilation of the ovine uterine circulation.

Estradiol-17beta (E2beta), a potent vasodilator, has its greatest effects on the uterine vasculature, blood flow (UBF) increasing > or = 10-fold. The mechanism(s) responsible for E2beta-induced vasodilation is unclear. We determined if nitric oxide (NO)-induced increases in cGMP modulate estrogen-induced increases in UBF, and if cyclooxygenase inhibition modifies E2beta responses. Nonpregnant (n = 15) and pregnant (n = 8) ewes had flow probes implanted on main uterine arteries and catheters in branches of the uterine vein and artery bilaterally for blood sampling and infusion of the NO synthase inhibitor L-nitro-arginine methyl ester (L-NAME), respectively. In nonpregnant ewes E2beta (1 microg/kg) caused parallel increases (P < 0.001) in UBF (15+/-3 to 130+/-16 ml/min) and uterine cGMP secretion (23+/-10 to 291+/-38 pmol/min); uterine venous cGMP also rose (4.98+/-1.4 to 9.43+/-3.2 pmol/ml; P < 0.001). Intra-arterial L-NAME partially inhibited increases in UBF dose-dependently (r = 0.66, n = 18, P < 0.003) while completely inhibiting cGMP secretion (P = 0.025). Indomethacin, 2 mg/kg intravenously, did not alter E2beta-induced responses. After E2beta-induced increases in UBF, intraarterial L-NAME partially decreased UBF dose dependently (r = 0.73, n = 46, P < 0.001) while inhibiting cGMP secretion (178+/-48 to 50+/-24 pmol/min; n = 5, P = 0.006); both were reversed by L-arginine. In pregnant ewes, E2beta increased UBF and venous cGMP (9.1+/-0.96 to 13.2+/-0.96 pmol/ml, P < 0.01); however, intraarterial L-NAME decreased basal cGMP secretion 66% (P = 0.02), but not UBF. Acute estrogen-induced increases in UBF are associated with NO-dependent increases in cGMP synthesis, but other mechanisms may also be involved. However, vasodilating prostanoids do not appear to be important. In ovine pregnancy NO is not essential for maintaining uteroplacental vasodilation.

Circulatory Changes in the Reproductive Tissues of Ewes during Pregnancy

The blood flows to reproductive organs were measured by means of radionuclide-labeled microspheres in 24 pregnant ewes with gestational ages ranging from 38 to 141 days. The microspheres were injected

Effect of estrogens on the uterine blood flow of oophorectomized ewes

Abstract Quantitative information about dilatation of uterine blood vessels after administration of estrogens is needed, e.g., the dose response of uterine blood flow to estrogens, whether different estrogens are equipotent in inducing vasodilation, the maximum obtainable blood flow to the nonpregnant uterus under maximum estrogen stimulation, and the related chain of biochemical events. The type of biological preparation developed and the results obtained thus far form the substance of this report.

Effect of estradiol-17β on blood flow to reproductive and nonreproductive tissues in pregnant ewes

The effect of estradiol-17beta (1 mug per kilogram) on regional blood flow and cardiac output was studied by means of radionuclide-labeled microspheres in 6 nonpregnant and 13 pregnant ewes five to seven days after operation. Estradiol caused vasodilation in myometrium, endometrium, and placental cotyledons throughout pregnancy, but these responses were significantly less than the fifteenfold increase seen in the nonpregnant uterine tissues. Significant vasodilation also occurred in the ovaries, cervix, vagina, uterine tubes, mammary gland, skin, and adrenal glands of pregnant ewes. Cardiac output increased by 14%. No significant change in uterine oxygen consumption was associated with the increase in blood flow to the pregnant uterus.

Effects of epinephrine on distribution of blood flow in the pregnant ewe

Seven pregnant ewes ranging from 85 to 140 days of gestation were infused with systemic doses of epinephrine and uterine arterial flow dose-response curves were determined. With a constant systemic infusion of epinephrine at a mean rate of 0.29 +/- 0.03 mug/Kg.-min., and the radionuclide lebeled microsphere method to measure arterial blood flow, a 38.5 per cent decrease in total uterine arterial blood flow was demonstrated while systemic pressure was unaltered. At this dose the reduction in endometrial blood flow was significantly greater (-58.7 per cent) than that in either the myometrium (-36.9 per cent) or placental cotyledons (-34.5 per cent) (p less than 0.025 and less than 0.005, respectively). There also occurred a decrease in blood flow to the mammary gland and the pancreas, whereas increased in blood flow to the skeletal muscle, adipose tissue, and spleen were documented. It is evident from this study that during the period of ovine pregnancy investigated, the vascular bed of all tissues comprising the pregnant uterus, including the placental cotyledons, are sensitive to the vasoconstrictive effects of epinephrine.

Metabolic Imprinting by Prenatal, Perinatal, and Postnatal Overnutrition: A Review

Epidemiological studies have suggested that metabolic programming is one of the critical factors contributing to the etiology of obesity as well as concurrent increase in related chronic diseases (e.g., type 2 diabetes and cardiovascular disease). Metabolic programming is the phenomenon whereby a nutritional stress/stimulus applied during critical periods of early development permanently alters an organisms physiology and metabolism, the consequences of which are often observed much later in life. The idea of metabolic programming originated from the fetal origins hypothesis proposed by Barker in which he suggested that disproportionate size at birth of the newborn due to an adverse intrauterine environment correlated well with an increased risk of adult-onset ill health outcomes (type 2 diabetes, hypertension, and cardiovascular disease). The fetal origins hypothesis, proposed by Barker, suggests that adequate nutrition during fetal development is critical. Overnutrition is a form of malnutrition that has increased in the United States over the past several decades in which nutrients are oversupplied relative to the amounts required for normal growth, development, and metabolism. Evidence for the effects of maternal obesity and overnutrition on metabolic programming is reviewed during critical prenatal, perinatal, and postnatal periods.

The differential leukocyte count in the assessment and outcome of early-onset neonatal group B streptococcal disease

The usefulness of the differential white blood cell count in distinguishing early-onset group B streptococcal disease from other causes of neonatal respiratory distress was studied in 45 infants with culture-proved infection. The initial diagnosis was hyaline membrane disease in 19 infants, wet lung syndrome 13, and other causes of respiratory distress in 13. Thirty-nine (87%) had abnormal absolute neutrophil counts, 25 with neutropenia and 14 with neutrophilia. The absolute immature neutrophil count was elevated in 19 infants (42%). Forty-one infants (91%) had an abnormal immature neutrophil to total neutrophil ratio. All infected infants were identified when both the absolute total neutrophil count and ratio were used. The differential white cell count appears to be a useful tool for screening infants presenting with respiratory distress in the first 48 hours of life and for separating early-onset group B streptococcal disease from other causes of neonatal respiratory distress.