Karen Dorman

Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization

Background Invasive techniques such as amniocentesis and cordocentesis are used for diagnosis and treatment in fetuses at risk for anemia due to maternal red-cell alloimmunization. The purpose of our study was to determine the value of noninvasive measurements of the velocity of blood flow in the fetal middle cerebral artery for the diagnosis of fetal anemia. Methods We measured the hemoglobin concentration in blood obtained by cordocentesis and also the peak velocity of systolic blood flow in the middle cerebral artery in 111 fetuses at risk for anemia due to maternal red-cell alloimmunization. Peak systolic velocity was measured by Doppler velocimetry. To identify the fetuses with anemia, the hemoglobin values of those at risk were compared with the values in 265 normal fetuses. Results Fetal hemoglobin concentrations increased with increasing gestational age in the 265 normal fetuses. Among the 111 fetuses at risk for anemia, 41 fetuses did not have anemia; 35 had mild anemia; 4 had moderate anemia; an...

Hemodynamic profile of severe pregnancy-induced hypertension

Cases of severe pregnancy-induced hypertension or eclampsia were studied in forty-five women by catheterization of the right side of the heart to define the presenting hemodynamic profile associated with this disorder. These women could not be easily categorized into one specific hemodynamic pattern. Most patients had high-normal to elevated systemic vascular resistance indices (mean 2726 +/- 120 dynes.sec.cm-5.m2). The mean cardiac index was 4.14 +/- 0.13 L.min-1.m2. The severity of hypertension was largely attributable to a disproportionate rise in the systolic component (mean 193 +/- 3 mm Hg) compared with diastolic blood pressure (mean 110 +/- 3 mm Hg). Women with eclampsia had significantly lower arterial blood pressure and systemic vascular resistance indices when compared with those of the rest of the study group. Analysis of Starling curves indicated that all patients had normal or hyperdynamic left ventricular function. A modest correlation was observed between central venous pressure and pulmonary capillary wedge pressure (r = 0.59). This disparity most likely results from the maintenance of normal to high cardiac output in the presence of an increased left ventricular afterload. The majority of patients with severe pregnancy-induced hypertension do have normal to high cardiac indices and pulmonary capillary wedge pressures accompanied by normal or hyperdynamic left ventricular function. This is true despite the presence of severe hypertension.

Follow-up of Children Exposed In Utero to 17 α-Hydroxyprogesterone Caproate Compared With Placebo

OBJECTIVE: To assess whether there are evident adverse effects of 17 &agr;-hydroxyprogesterone caproate after in utero exposure. METHODS: This study evaluated surviving children of mothers who participated in a multicenter placebo-controlled trial of weekly intramuscular 17 &agr;-hydroxyprogesterone caproate, with a 2:1 allocation to 17 &agr;-hydroxyprogesterone caproate and placebo, respectively. The guardian was interviewed about the child’s general health. Children underwent a physical examination and developmental screen with the Ages and Stages Questionnaire. Gender-specific roles were assessed with the Preschool Activities Inventory. RESULTS: Of 348 eligible surviving children, 278 (80%) were available for evaluation (194 in the 17 &agr;-hydroxyprogesterone caproate group and 84 in the placebo group). The mean age at follow-up was 48 months. No significant differences were seen in health status or physical examination, including genital anomalies, between 17 &agr;-hydroxyprogesterone caproate and placebo children. Scores for gender-specific roles (Preschool Activities Inventory) were within the normal range and similar between 17 &agr;-hydroxyprogesterone caproate and placebo groups. CONCLUSION: 17 &agr;-hydroxyprogesterone caproate seems to be safe for the fetus when administered in the second and third trimesters. LEVEL OF EVIDENCE: II

Cardiovascular alterations in severe pregnancy-induced hypertension: Relationship of central venous pressure to pulmonary capillary wedge pressure

The relationship between central venous pressure and pulmonary capillary wedge pressure was studied in 18 patients with severe pregnancy-induced hypertension. Although statistically a linear relationship for the group as a whole could be identified, analysis on a case-by-case basis revealed different results. In 10 patients, a linear correlation between central venous pressure and pulmonary capillary wedge pressure was observed. However, accurate prediction of pulmonary capillary wedge pressure from central venous pressure was not possible even in this group because of large interindividual variations. In seven patients no correlation between central venous pressure and pulmonary capillary wedge pressure could be identified. In the last patient a curvilinear relationship existed between central venous pressure and pulmonary capillary wedge pressure. Additionally, in five cases of pulmonary edema, a negative gradient of colloid osmotic pressure to pulmonary capillary wedge pressure gradient was observed. Our data suggest that central venous pressure is not a clinically reliable predictor of pulmonary capillary wedge pressure.

An Endothelial Nitric Oxide Synthase Gene Polymorphism is Associated with Preeclampsia

OBJECTIVE We sought to test the hypothesis that a polymorphism of the endothelial nitric oxide synthase gene (NOS3) is associated with preeclampsia. METHODS We collected and performed polymerase chain reaction (PCR) on genomic DNA from pregnant patients with and without preeclampsia. Patient history and clinical course were evaluated. MAIN OUTCOME MEASURE(S) Frequency of the intron 4 polymorphism of NOS3 (designated allele A) among patients with preeclampsia compared with controls. Clinical features of patients with preeclampsia and the A allele compared with those patients with preeclampsia who did not have the A allele. RESULTS The frequency of the A allele was 0.10 among controls versus 0.39 among patients with preeclampsia (p < 0.01). The odds ratio of developing preeclampsia when at least one A allele was present was 6.5 [95% confidence interval (CI): 2.1-19.7]. After adjusting for ethnic variation, the odds ratio increased to 7.2 (95% CI: 2.0-25.5). Among patients with preeclampsia, systolic blood pressure at the time of admission was higher for patients with at least one A allele compared with patients homozygous for the B allele (168 versus 156 mm Hg; p = 0.03), independent of gestational age (p = 0.01). CONCLUSION These data provide evidence for an association between NOS3 and preeclampsia. In defined ethnic groups, this NOS3 may offer predictive information regarding the subsequent development of preeclampsia and its clinical course.

Plasma choline in normal newborns, infants, toddlers, and in very-low–birth-weight neonates requiring total parenteral nutrition☆

Choline deficiency is associated with hepatic abnormalities in adult volunteers and patients administered total parenteral nutrition (TPN). Preliminary investigation has suggested that plasma-free choline concentration (PFCh) is greater in neonatal animals, including humans, than in adults. The aims of this study were to determine the normal PFCh and phospholipid-bound choline concentration (PPLBCh) for newborns, infants, and toddlers and to determine the change during TPN. We also sought to determine the degree of fetal choline extraction, the relation between maternal and newborn plasma choline concentrations, and the relation between plasma choline status and normal newborn length, weight, and gestational age. Blood samples were obtained from 104 full-term newborns in two centers (Ben Taub and Maimonides), 25 mothers, 21 normal infants aged 20.3 +/- 11.8 wk, 12 normal infants aged 62.4 +/- 3.9 wk, and 14 preterm infants (gestational age = 28.9 +/- 2.2 wk) who required TPN. The vein PFChs were 28.1 +/- 13.0 nmol/mL (Ben Taub) and 68.1 +/- 16.9 nmol/mL (Maimonides). The artery PFChs were 27.1 +/- 13.0 nmol/mL (Ben Taub) and 57.9 +/- 11.6 nmol/mL (Maimonides). The vein PPLChs were 1004.7 +/- 246.6 nmol/mL (Ben Taub) and 1121.2 +/- 289.6 nmol/mL (Maimonides). The artery PPLChs were 1065.7 +/- 469.3 nmol/mL (Ben Taub) and 1106.9 +/- 285.8 nmol/mL (Maimonides). The vein-minus-artery differences for PFCh were 1.0 +/- 9.7 nmol/mL (Ben Taub) and 10.2 +/- 10.9 nmol/mL (Maimonides). The vein-minus-artery differences for PPLCh were -51.9 +/- 398.2 nmol/mL (Ben Taub General Hospital, Houston, Texas) and 14.4 +/- 254.3 nmol/mL (Maimonides, New York, New York). Maternal venous PFCh was 8.4 +/- 3.1 nmol/mL. Maternal venous PPLCh was 2592.1 +/- 584.0 nmol/mL (range = 1227.8-3729.0). Maternal venous PFCh correlated with newborn arterial PFCh (r = 0.53, P < 0.05) but not with newborn venous PFCh. No correlation was seen between maternal venous and newborn PPLCh. No significant differences were seen in PPLCh or choline extraction in Ben Taub versus Maimonides patients, although PFCh was significantly greater in the newborns from Maimonides (P < 0.05). The mean venous PFCh and PPLCh in the preterm infants before beginning TPN was 21.2 +/- 6.3 and 1366.8 +/- 339.1 nmol/mL, respectively. Just before initiation of tube feeding (4.0 +/- 2.7 d after TPN had been started), mean venous PFCh and PPLCh was 18.4 +/- 5.3 and 2251.8 +/- 686.9 nmol/mL, respectively. When TPN was discontinued and tube feeding increased to goal, after 10.8 +/- 10.4 d, venous PFCh and PPLCh was 22.6 +/- 8.7 and 2072.5 +/- 540.6 nmol/mL, respectively. Venous PFCh and PPLCh was 13.4 +/- 2.5 and 1827.5 +/- 327.0 nmol/mL, respectively in the older infant group. In conclusion, newborn PFCh is significantly greater than PFCh in adults but falls to adult levels within the first year of life. Low maternal PFCh may be associated with low newborn PFCh. Normal newborn plasma choline status has no bearing on intrauterine growth, although the role of maternal choline deficiency in underweight newborns is unknown. Newborn PPLCh is substantially below that of adults, which suggests its use in membrane synthesis during growth.

Role of intravenous nitroglycerin in the treatment of severe pregnancy-induced hypertension complicated by pulmonary edema

Intravenous nitroglycerin would appear to be an ideal agent for the treatment of severe pregnancy-induced hypertension complicated by cardiogenic pulmonary edema. Nitroglycerin infusion effectively reduces preload by venous dilatation and, at higher doses, results in arterial vasodilatation. Because of these pharmacologic properties, the effects of intravenous nitroglycerin were studied in three patients with severe pregnancy-induced hypertension complicated by pulmonary edema. The major cardiovascular effects of nitroglycerin were to reduce the mean pulmonary capillary wedge pressure from 27 +/- 4 to 14 +/- 6 mm Hg, which result in a change in the colloid osmotic pressure to pulmonary capillary wedge pressure gradient from -10 to 2 mm Hg. No significant changes occurred in heart rate, central venous pressure, or cardiac index. Analysis of oxygen-related parameters revealed a significant (p less than 0.05) increase in oxygen delivery and extraction accompanied by a 53% increase in oxygen consumption. The changes in oxygen-related variables appeared to be secondary to a fall in mixed venous oxygen tension from 39 +/- 4 to 33 +/- 1 torr. These changes occurred without any significant improvement in arterial oxygen tension. We conclude that while intravenous nitroglycerin expeditiously corrects the hydrostatic derangements of pulmonary edema seen in pregnancy-induced hypertension, a rapid improvement in arterial oxygenation does not occur.

Use of the World Wide Web in research: Randomization in a multicenter clinical trial of treatment for twin-twin transfusion syndrome

OBJECTIVE To describe the process involved in using the World Wide Web to coordinate a randomized, multicenter international trial of treatment for twin-twin transfusion syndrome. METHOD A Web site was designed by members of the research team, a Web consultant, and a senior computer programmer. The original intent was to provide patient randomization only, but the Web site later was designed so that centers could download a data collection form. Data could be entered directly into the Web site and subsequently imported into a database at the coordinating center. EXPERIENCE The Web site has been active for 3 years, with 13 participating centers and 31 patients enrolled. COMMENT Use of the World Wide Web to coordinate an international, multicenter trial is an efficient method. Although there are many benefits, the most obvious is the capability to initiate and conduct a large international trial at minimal cost.

A Simple Method to Estimate Volume for Fetal Intravascular Transfusions

We derived a constant termed the transfusion coefficient to simplify the estimation of the fetal intravascular transfusion volume. The product of the estimated fetal weight (g) and 0.02 (transfusion coefficient), estimates the transfusion volume (ml) required to increase the fetal hematocrit by approximately 10 percentage points. Our estimation was comparable to Mandelbrot’s technique and better than Plecas’ method for estimating fetal transfusion volumes. Utilizing the transfusion coefficient to estimate the intravascular transfusion volume for an anemic fetus is simple, rapid and accurate.

An animal model for hemolytic disease of the fetus and newborn. II. Fetal effects in New Zealand rabbits

OBJECTIVE The addition of ultrasonography and ultrasonographically directed fetal blood sampling was attempted in an effort to study the fetal effects of red blood cell alloimmunization in a rabbit model. STUDY DESIGN Nineteen New Zealand does were alloimmunized to incompatible red blood cells. Sensitized does were bred twice, once with a homozygous buck of incompatible blood type and once with a homozygous buck of compatible blood type. Ultrasonographic examinations were performed on days 20 and 27 of gestation (term 28 to 31 days). Fetal blood sampling was undertaken on day 27 of gestation, and hematologic data were compared between compatible and incompatible litters. RESULTS A total of 41 pregnancies occurred in 19 does. Fetal hemoglobin was higher in the compatible litters (9.7 gm/dl vs 5.8 gm/dl, p < 0.001), whereas no difference could be detected between the respective reticulocyte counts (31.9 vs 36.0/100 red blood cells, p = 0.2). Hydrops fetalis was noted in none of 18 compatible litters versus 12 of 19 incompatible litters (p < 0.01). CONCLUSION A disease analogous to human hemolytic disease of the newborn can be induced in the rabbit fetus.