John J. Botti

Gastric dysrhythmias and nausea of pregnancy.

Gastric dysrhythmias have been recorded from patients with a variety of nausea syndromes. The aim of this study was to measure gastric myoelectric activity in women with and without nausea during the first trimester of pregnancy. In 32 pregnant women gastric myoelectric activity was recorded for 30–45 min with cutaneous electrodes that yielded electrogastrograms (EGGs). Frequencies of the EGG waves were analyzed visually and by computer. Subjects rated their nausea at the time of EGG recording on a visual analog scale with 0 representing no nausea and 300 mm severe nausea. Gastric dysrhythmias were found in 26 pregnant subjects: Seventeen had tachygastrias (EGG frequencies of 4–9 cpm),five had 1- to 2-cpm EGG waves, and four had flat-line patterns. Mean nausea scores of the subjects with tachygastrias, 1- to 2-cpm, and flat-line patterns were 64.8±13, 93.4±23, and 77.2±36, respectively. Six pregnant subjects had normal 3-cpm EGG patterns, and their nausea scores averaged 2.8±1.1 (P<0.05 compared with nausea scores in subjects with tachygastrias, 1- to 2-cpm, and flat-line rhythms). Six subjects with gastric dysrhythmias during pregnancy were restudied after delivery; each of these subjects had normal 3-cpm EGG patterns and none had nausea. Thus, gastric dysrhythmias are objective pathophysiologic events associated with symptoms of nausea reported during the first trimester of pregnancy.

Neutrophil attractant/activating peptide-1/interleukin-8: Association with histologic chorioamnionitis, preterm delivery, and bioactive amniotic fluid leukoattractants†‡

OBJECTIVES The goals of this study were (1) to determine immunoreactive neutrophil attractant/activating peptide-1/interleukin-8 levels in amniotic fluid from patients with preterm labor and (2) to compare neutrophil attractant/activating peptide-1/interleukin-8 levels, amniotic fluid culture, Gram stain, and the leukotaxis bioassay for their ability to predict histologic chorioamnionitis and clinical outcome. STUDY DESIGN Amniotic fluid was collected by amniocentesis from 55 patients with idiopathic preterm labor and three patients with preterm labor and clinical chorioamnionitis. Gram stain, culture (aerobic, anaerobic, and Mycoplasma species), leukotaxis bioassay, and a commercially available neutrophil attractant/activating peptide-1/interleukin-8 enzyme-linked immunosorbent assay (sensitivity 1 ng/ml) were performed on the amniotic fluid samples. Placentas and chorionic membranes were evaluated for evidence of histologic chorioamnionitis in patients delivered preterm. RESULTS All patients with detectable leukoattractants by the leukotaxis bioassay had neutrophil attractant/activating peptide-1/interleukin-8 levels above the threshold of the assay. The presence of amniotic fluid neutrophil attractant/activating peptide-1/interleukin-8 is a more sensitive marker for histologic chorioamnionitis and delivery before 34 weeks than is amniotic fluid culture (100% vs 59%, p < 0.01; and 95% vs 56%, p < 0.01, respectively). Also, of patients in idiopathic preterm labor those without amniotic fluid leukoattractants (group 1) had the lowest amniotic fluid levels, followed by patients with amniotic fluid leukoattractants and a negative culture (group 2) and patients with amniotic fluid leukoattractants and a positive culture (group 3) who had the highest levels (group 1 vs group 2, p < 0.001; group 2 vs group 3, p < 0.01). CONCLUSIONS Amniotic fluid neutrophil attractant/activating peptide-1/interleukin-8, like the leukotaxis assay, is an accurate antepartum predictor of histologic chorioamnionitis and subsequent early delivery in patients with preterm onset of labor. This study supports the role of neutrophil attractant/activating peptide-1/interleukin-8 in the recruitment of neutrophils into chorionic membranes and placenta during developing intrauterine infection.

Erythropoietin stimulates a rise in intracellular free calcium concentration in single early human erythroid precursors.

Erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate the differentiation and proliferation of erythroid cells. To determine the cellular mechanism of action of these growth factors, we measured changes in intracellular free calcium concentration [( Cac]) in single human erythroid precursors in response to recombinant erythropoietin and GM-CSF. [Cac] in immature erythroblasts derived from cultured human cord blood erythroid progenitors was measured with fluorescence microscopy digital video imaging. When stimulated with erythropoietin, [Cac] in the majority of erythroblasts increased within 3 min, peaked at 5 min, and returned toward baseline at 10 min. The percentage of cells that responded to erythropoietin stimulation increased in a dose-dependent manner. Additional stimulation with GM-CSF in cells previously exposed to erythropoietin resulted in a second [Cac] increase. Immature erythroblasts treated with GM-CSF followed by erythropoietin responded similarly to each factor with a rise in [Cac]. The source of transient calcium is intracellular since erythroblasts were incubated in medium devoid of extracellular calcium. Our observations suggest that changes in [Cac] may be an intracellular signal that mediates the proliferative/differentiating effect of hematopoietic growth factors.

Improving women's preconceptional health: long-term effects of the Strong Healthy Women behavior change intervention in the central Pennsylvania Women's Health Study.

PURPOSE To investigate the long-term (6- and 12-month) effects of the Strong Healthy Women intervention on health-related behaviors, weight and body mass index (BMI), and weight gain during pregnancy. Strong Healthy Women is a small-group behavioral intervention for pre- and interconceptional women designed to modify key risk factors for adverse pregnancy outcomes; pretest-posttest findings from a randomized, controlled trial have been previously reported. The following questions are addressed: 1) were significant pretest-posttest changes in health-related behaviors (previously reported) maintained over the 12-month follow-up period; 2) did the intervention impact weight and BMI over the 12-month follow-up period; and 3) did the intervention impact pregnancy weight gain for those who gave birth during the follow-up period? METHODS Data are from 6- and 12-month follow-up telephone interviews of women in the original trial of the Strong Healthy Women intervention (n = 362) and from birth records for singleton births (n = 45) during the 12-month follow-up period. Repeated measures regression was used to evaluate intervention effects. MAIN FINDINGS At the 12-month follow-up, participants in the Strong Healthy Women intervention were significantly more likely than controls to use a daily multivitamin with folic acid and to have lower weight and BMI. The interventions effect on reading food labels for nutritional values dropped off between the 6- and 12-month follow-up. Among those who gave birth to singletons during the follow-up period, women who participated in the intervention had lower average pregnancy weight gain compared with controls. Although the intervention effect was no longer significant when controlling for pre-pregnancy obesity, the adjusted means show a trend toward lower weight gain in the intervention group. CONCLUSION These findings provide important evidence that the Strong Healthy Women behavior change intervention is effective in modifying important risk factors for adverse pregnancy outcomes and may improve an important pregnancy outcome, weight gain during pregnancy. Because the intervention seems to help women manage their weight in the months after the intervention and during pregnancy, it may be an effective obesity prevention strategy for women before, during, and after the transition to motherhood.

Successful use of argatroban during the third trimester of pregnancy: case report and review of the literature.

Direct thrombin inhibitors are commonly used anticoagulants in patients with known or suspected heparin‐induced thrombocytopenia (HIT). All three direct thrombin inhibitors available in the United States—argatroban, bivalirudin, and lepirudin—are pregnancy category B drugs based on animal studies, but little data are available on the safety of these agents during human pregnancy. Whereas several case reports support the safe use of lepirudin, only one case report has been published with argatroban and none with bivalirudin. We describe a 26‐year‐old pregnant woman with portal vein thrombosis and thrombocytopenia treated with argatroban for possible HIT during her last trimester. An argatroban infusion was started at 2 μg/kg/minute during her 33rd week of pregnancy, with the dosage titrated based on the activated partial thromboplastin time; infusion rates ranged from 2–8 μg/kg/minute. Treatment continued until her 39th week of pregnancy, when labor was induced. Argatroban therapy was discontinued 7 hours before epidural anesthesia. The patient successfully delivered a healthy male newborn, devoid of any known adverse effects from argatroban. The infant was found to have a small ventricular septal defect and patent foramen ovale at birth, but it is unlikely that these were caused by argatroban since organogenesis occurs in the first trimester. Even though the cause of this patients thrombocytopenia was later determined to be idiopathic thrombocytopenic purpura, this is an important case that adds to the literature on use of argatroban during pregnancy.

Alterations in Transfer and Lipid Distribution of Arachidonic Acid in Placentas of Diabetic Pregnancies

Placental tissue from nondiabetic term pregnancies and pregnancies complicated by maternal insulindependent diabetes mellitus (IDDM) was perfused in vitro to compare the transfer and lipid distribution of arachidonic acid (AA). Radiolabeled albumin-bound AA was administered into the maternal afferent circulation, and samples of fetal and maternal effluent were collected at 10-min intervals. Perfused placental tissue was collected at the end of each experiment. The effluent was analyzed for total radioactivity, and extracts were subjected to thin-layer chromatography for the assessment of radioactivity associated with various lipid fractions. Placental AA uptake was significantly increased in perfused tissue from diabetic pregnancies (0.88 vs. 1.72 nM · min−1 · g−1 in nondiabetic and IDDM, respectively; P < 0.01), as was AA transfer (0.22 vs. 0.42 ml/min in nondiabetic and IDDM, respectively; P < 0.01). However, transfer of the highly diffusible marker substance antipyrine was significantly reduced in IDDM placentas (1.79 vs. 2.49 ml/min in IDDM and nondiabetic, respectively; P < 0.01). Compared with nondiabetic placentas, incorporation of AA into triglyceride was significantly increased in both maternal and fetal effluents and in placental tissue from IDDM pregnancies, whereas the percentage of AA remaining unesterified was reduced in both placental tissue and fetal effluent. Incorporation of AA into phosphoglycerides was significantly reduced in placental tissue but increased in fetal effluent in placentas from IDDM pregnancies. The results of these studies suggest that transfer and lipid distribution of AA are significantly altered in placentas from IDDM pregnancies. These findings may be relevant to the increased incidence of abnormal fetal growth and development associated with IDDM pregnancies.

Eicosanoid production and transfer in the placenta of the diabetic pregnancy

The metabolism of arachidonic acid (AA) and the transfer of its metabolites was determined in in vitro perfused placental tissue from normal pregnancies and those complicated by maternal insulin-dependent diabetes mellitus (IDDM). 14C-labelled AA was recirculated in the fetal circulation for 60 min while 3H-AA was recirculated in the maternal circulation. Placental effluent was subjected to high performance liquid chromatography (HPLC) and analysis of dual-label scintillation counts. Placentae from IDDM pregnancies converted 3-6 times more radiolabelled AA to eicosanoids than did normal placentae. In addition, the transfer of eicosanoids into the opposing circulation was doubled in placentae from IDDM pregnancies compared to normal placentae. The predominant direction of eicosanoid transfer in both groups of placentae was in the fetal-to-maternal direction. The relative amounts of eicosanoids produced was also altered in placentae from IDDM pregnancies. Increased amounts of thromboxane (Tx) B2 and hydroxyeicosatetraenoic acids (HETEs) were present in both circulations of placentae from IDDM pregnancies. Levels of 6-keto prostaglandin F1a (6KPGF1a) were significantly reduced in both circulations in placentae from IDDM pregnancies. Thus, the ratio of TxA2 to PGI2 and the ratio of HETEs to PGI2 were both significantly increased in placentae from IDDM pregnancies. These results suggest an imbalance in eicosanoid production which may be relevant to abnormal placental structure and function in IDDM pregnancies.

Portal venous blood flow distribution to liver and ductus venosus in newborn lambs

Changes in the distribution of portal venous blood flow to the left and right lobes of the liver and through the ductus venosus were determined from before birth through 9 days of age in 25 chronically catheterized fetal and newborn lambs. Blood flow distribution was calculated by means of the radionuclide-labeled microsphere technique. With umbilical cord clamping portal venous blood flow distribution to the right lobe of the liver decreased when compared to that in the term fetus; distribution to the left lobe and ductus venosus increased. More than 50% of portal blood flow was shunted through the ductus venosus during the first hour after birth. Ductus venosus shunts of at least 25% of total portal blood flow were noted in half the lambs between the second and sixth days of life. Portal venous distribution to the right lobe was inversely related to the fraction of portal blood flow shunted through the ductus venosus. The ratio of right lobe weight to total liver weight was significantly correlated with the ratio of right lobe flow to total liver flow (r = 0.73; P less than 0.001). The conclusion is that large and persistent ductus venosus shunts are normal during the first postnatal week in lambs.

Amniotic fluid leukotaxis assay as an early indicator of chorioamnionitis

A characteristic feature of histologic chorioamnionitis caused by ascending infection is the amniotropism displayed by polymorphonuclear leukocytes in the placental membranes. We tested the hypothesis that amniotic fluid from patients with histologic chorioamnionitis and intact membranes without clinical infection contains leukoattractants detectable by an in vitro leukotactic assay. Leukoattractants were detected in 13 cases (87%) and absent in 2 cases (13%) with histologic chorioamnionitis (p less than 0.005). The two cases with histologic chorioamnionitis that had negative leukotaxis were classified as stage l/mild severity. A positive leukotactic response was a better predictor of histologic chorioamnionitis (87%) than positive Gram stain (33%), amniotic fluid culture (53%), gas-liquid chromatography (40%), or a combination of these three methods (60%). These results suggest that demonstration of leukoattractants in amniotic fluid is an earlier and more sensitive predictor of chorioamnionitis than is presently available.

Nonimmunologic Hydrops Fetalis: A Review of 19 Cases

Nineteen cases of nonimmunologic hydrops fetalis occurring during a nine‐year period were reviewed. The pregnancies were complicated by hydramnios (78%) and preterm delivery (84%). Hydramnios appears to be the most useful indicator of the pregnancy at risk; its occurrence should prompt ultrasonographic investigation for evidence of hydrops. Modalities available for antenatal diagnosis of underlying fetal abnormalities include amniocentesis, serologic tests, fetal cardiac monitoring, radiography, hemoglobin electrophoresis and glucose tolerance testing. A specific cause for the hydrops may not be detectable (42% of our cases were idiopathic). Management of affected pregnancies is influenced by the frequent occurrence of fetal asphyxia and premature delivery. Outcome is poor: only 32% of the babies survived beyond the neonatal period. Symptomatic treatment for the neonate includes fluid restriction, maintenance of blood sugar, support of ventilation and attention to the complications of asphyxia.