Robert Egerman

Multicenter randomized trial of cerclage for preterm birth prevention in high-risk women with shortened midtrimester cervical length

OBJECTIVE The objective of the study was to assess cerclage to prevent recurrent preterm birth in women with short cervix. STUDY DESIGN Women with prior spontaneous preterm birth less than 34 weeks were screened for short cervix and randomly assigned to cerclage if cervical length was less than 25 mm. RESULTS Of 1014 women screened, 302 were randomized; 42% of women not assigned and 32% of those assigned to cerclage delivered less than 35 weeks (P = .09). In planned analyses, birth less than 24 weeks (P = .03) and perinatal mortality (P = .046) were less frequent in the cerclage group. There was a significant interaction between cervical length and cerclage. Birth less than 35 weeks (P = .006) was reduced in the less than 15 mm stratum with a null effect in the 15-24 mm stratum. CONCLUSION In women with a prior spontaneous preterm birth less than 34 weeks and cervical length less than 25 mm, cerclage reduced previable birth and perinatal mortality but did not prevent birth less than 35 weeks, unless cervical length was less than 15 mm.

Cerebrovascular disorders complicating pregnancy - Beyond eclampsia

OBJECTIVE Our purpose was to investigate the problems encountered in the diagnosis and management of cerebrovascular disorders associated with pregnancy and the puerperium. STUDY DESIGN Pregnancies complicated by cerebrovascular disorders were identified by retrospective chart review (1985 to 1995). Events associated with trauma, neoplasm, drug ingestion, and infection were excluded. RESULTS The study population comprised 24 women with a variety of cerebrovascular disorders: 14 with infarction (5 arterial, 9 venous), 6 with intracranial hemorrhage (3 anatomic malformation, 3 unknown etiology), 3 with hypertensive encephalopathy, and 1 with an unruptured aneurysm. Blood pressure reflected physical condition at presentation and did not predict diagnosis or outcome except in the 3 women with hypertensive encephalopathy. Only 4 of 14 women with infarction and 1 of 6 with intracranial hemorrhage had a diastolic blood pressure > or = 110 mm Hg. Presumption of eclampsia delayed the diagnosis in 10 women (41.7%). In addition, patient delay in seeking medical attention complicated 10 cases. After review, none of the adverse maternal outcomes were deemed preventable by earlier physician intervention. Seven maternal deaths occurred (29.2%). Neonatal outcome was related to the gestational age and the maternal condition at presentation. CONCLUSION Cerebrovascular disorders are an uncommon and unpredictable complication of pregnancy that are associated with substantial maternal and fetal mortality. Suspected eclampsia unresponsive to magnesium sulfate therapy warrants an immediate neuroimaging study. Interestingly, in women with intracranial hemorrhage, severe hypertension was not an associated predictive factor.

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in pregnancy: Review of 11 cases

OBJECTIVE Little information exists regarding thrombotic thrombocytopenic purpura and hemolytic uremic syndrome during pregnancy. We report a series of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome complicating pregnancy, with emphasis on diagnosis and management of this rare disorder. STUDY DESIGN Between January 1988 and February 1996, 11 women with either thrombotic thrombocytopenic purpura (n = 8) or hemolytic uremic syndrome (n = 3) were evaluated. Clinical and laboratory findings and maternal and neonatal outcomes were recorded from the medical records. RESULTS Eight of the 11 women were in the third trimester or peripartum period, and three were seen before fetal viability. Treatment included fresh-frozen plasma in all women, plasmapheresis (n = 8), packed red blood cells (n = 9), and platelet transfusions (n = 5); 1 patient required splenectomy. There were two maternal deaths. Of the 9 surviving women, 4 had chronic renal disease, 1 of whom also had residual neurologic deficit. Preterm delivery occurred in 5 of 8 pregnancies continuing beyond 20 weeks. Indications for delivery in these 5 women included worsening maternal medical disease, nonreassuring fetal testing, and spontaneous preterm labor. Six of 8 women with viable fetuses underwent cesarean delivery. These 6 infants were born in good condition without thrombocytopenia. Of the remaining 2 infants delivered vaginally, one was healthy at 35 weeks and the other was stillborn. CONCLUSION Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome complicating pregnancy is associated with high maternal mortality and long-term morbidity. Preterm delivery and intrauterine fetal death are frequent complications of these pregnancies. Improved survival after this disorder has been attributed to aggressive treatment with plasma transfusion or plasmapheresis.

Dehydroepiandrosterone Attenuates Study‐Induced Declines in Insulin Sensitivity in Postmenopausal Womena

Dehydroepiandrosterone (DHEA) and its sulfated congener dehydroepiandrosterone sulfate (DHEAS) may play a rolc in the regulation of immune competence’ and insulin sensitivity2 and also may be cardioprotective.2 Age-related declines in adrenocortical androgen secretion, independent of cortisol, may thus contribute to the increased prevalence of insulin resistance in the elderly. In rodents, DHEA decreases the severity of genetic and induced diabetes2 In humans, amelioration of diabetes in a DHEA-supplemented patient has been described.3 Additionally, 17-hour DHEA infusions enhance postreceptor insulin a ~ t i o n , ~ and 3 weeks of oral DHEA increases T-lymphocyte insulin binding and degradation.z We have defined a low dosc preparation of DHEA that recreates the reproductive age adrenal androgen milieu in elderly subjects.? We hypothesize that with this system, DHEA supplementation will decrease insulin resistance in an androgen-deficient population of postmenopausal women.

A comparison of the bioavailability of oral and intramuscular dexamethasone in women in late pregnancy

Objective To compare the bioavilability of oral and intramuscular (IM) dexamthasonei in third-trimester pregnant women. Methods Oral and IM dexamethasone levels were compared in a randomized, parallel, crossover bioavailability study involving 11 gravid women in the third trimester of pregnancy. Subjects were randomized to receive either 6 mg of IM or 8 mg of oral dexamethasone. The following week, the alternative regimen was administered. Serial blood samples were obtained after drug administration. Dexamethasone concentrations were measured by radioimmunoassay. Total area under the curve was compared for the oral and IM groups using a paired t test. Results Eight of the 11 women completed the study through 12 hours; all 11 women completed the study through 6 hours. Among the 11 women, peak levels of dexamethasone occurred 30 minutes after IM injection (mean ± standardf deviation, 101.7 ± 19.2 ng/mL) and 120 minutes after oral administration (65.9 ± 20.5 ng/mL). Area under the curve did not differ significantly between those receiving IM dexamethasone (258.3 ± 50.0 ng/minu/mL) when measured 6 hours after administration of the drug. Terminal half-lives were similar in the IM and oral groups. Similar findings were noted among the eight women who were studied through 12 hours. This study had a power of 87% to detect a 20% difference in area under the curve between the two groups. Conclusion The bioavailability of 8 mg of oral dexamethasone is similar to that of a 6-mg IM dose, as determined by the area under the curve.

Perinatal outcomes in pregnancies managed with antenatal insulin glargine.

We compared perinatal outcomes in pregnancies in which insulin glargine was used in the management of patients with pregnancies in which standard insulin therapy was used at a single institution. A retrospective analysis of 114 pregnant patients with diabetes (pregestational or gestational) managed at a single center between January 2004 and August 2006 was undertaken. Sixty-five patients managed with insulin glargine were compared with 49 patients managed with neutral protamine Hagedorn (NPH) insulin. Both groups were also treated with short-acting insulin (either regular, lispro, or aspart insulin). Maternal age, parity, prepregnancy weight, body mass index, duration of diabetes, hemoglobin A (1C) (at entry and final recorded) and gestational age at entry were similar for each group (glargine and NPH). Thirty patients had gestational diabetes (18 glargine and 12 NPH); there were no differences in numbers of patients in higher-order Whites classification between the two groups. Cesarean section for obstetric reasons included labor abnormalities, malpresentation, fetal distress, and suspected macrosomia. There were no differences in gestational age at delivery, birth weight, preeclampsia, or frequency of cesarean section (total or for obstetric reasons). The frequency of shoulder dystocia was higher in the NPH group. Regarding neonatal outcomes, gestational age at delivery, birth weight, Apgar scores, admission to the neonatal intensive care unit, respiratory distress syndrome, hypoglycemia, and congenital anomalies were similar between the two groups. From this retrospective analysis, no adverse maternal or neonatal effects were seen from maternal administration of insulin glargine. A larger multicenter study is needed to confirm these findings. This preliminary report suggests that use of insulin glargine during pregnancy can be considered if maternal metabolic control is suboptimal using the standard split-mix regimen.

Neuropeptide Y and nitrite levels in preeclamptic and normotensive gravid women

OBJECTIVES Vascular tone is controlled largely by the sympathetic nervous system and is modulated by neuropeptide Y. Preeclampsia is linked to sympathetic overactivity. Nitric oxide can cause vasorelaxation of vessels or decrease sympathetic outflow by activating the baroreceptor reflex. Our purpose in this study was to compare serum levels of neuropeptide Y and nitrite levels in normotensive and preeclamptic gravid women. STUDY DESIGN Twelve preeclamptic and 12 normotensive women matched for race, body mass index, parity, and gestational age were studied. Neuropeptide Y was measured by using a commercial radioimmunoassay. Nitric oxide was converted to nitrite by using metallic cadmium, and nitrite levels were determined spectrophotometrically by using a colorimetric assay. Data are presented as mean +/- SEM and were compared by using a t test. RESULTS Neuropeptide Y levels were similar among preeclamptic and normotensive gravid women (33.8 +/- 3.0 and 32.2 +/- 3 pg/mL, respectively). Similarly, there were no differences in nitrite concentrations between preeclamptic and normotensive patients (11.6 +/- 0.8 vs 11.2 +/- 0.4 micromol/L, respectively). We also examined the ratios of neuropeptide Y and nitrite and found no correlation between preeclamptic and normotensive women. CONCLUSION Peripheral levels of neuropeptide Y or nitrite do not correlate with preeclampsia. Assessment of sympathetic overactivity in preeclampsia requires an alternate model.

Comparison between oral and intramuscular dexamethasone in suppressing unconjugated estriol levels during the third trimester

OBJECTIVES Unconjugated estriol production depends on fetal adrenal androgen precursors. Fetal exposure to exogenous glucocorticoids results in adrenal suppression with a subsequent decrease in maternal serum unconjugated estriol levels. We compared the efficacy between oral and intramuscular dexamethasone in maternal serum unconjugated estriol suppression at 48 hours after the initial dose among women at risk for preterm delivery. STUDY DESIGN Twenty-four gravidas at risk for preterm delivery were randomized to receive either 6 mg intramuscular or 8 mg oral dexamethasone every 12 hours for a total of 4 doses. Blood samples (9 mL) were obtained before the initial dexamethasone administration and again after the fourth dose. Serum was separated and frozen at -70 degreesC and subsequently underwent batch analysis. Unconjugated estriol levels were determined by radioimmunoassay with intra-assay and interassay coefficients of variation of 7.9% and 5.5%, respectively. All values are reported as mean +/- SD. The primary statistical analysis was a t test, with P <.05 considered significant. RESULTS At the time of dexamethasone administration, gestational ages in both groups were similar. Predexamethasone and postdexamethasone unconjugated estriol levels were also similar between the intramuscular and oral groups (5.39 +/- 3.99 vs 1.80 +/- 2.49 ng/mL and 6.05 +/- 3.00 vs 1.61 +/- 1.03 ng/mL, respectively, P >.05). No difference in percent decrease in unconjugated estriol levels was found between the intramuscular (0.67 +/- 0.24) and oral (0.65 +/- 0.39) groups. CONCLUSION Oral dexamethasone (8 mg) produces similar maternal serum unconjugated estriol suppression compared with intramuscular dexamethasone (6 mg) when evaluated 48 hours after administration.

Autonomic and Enteric Nervous System Dysfunction May Play a Role in Hyperemesis Gravidarum

Background Nausea and vomiting, seen in 70-85% of all pregnancies, becomes intractable in hyperemesis gravidarum (HG). We aimed to investigate the relationship between HG and autonomic nervous system functioning and gastric electrical activity. Methods Twenty-seven pregnant patients, 21 with HG and six normal, were studied with sympathetic adrenergic; percent vasoconstriction (%VC) and postural adjustment ratio (PAR); parasympathetic vagal cholinergic functions by R-to-R intervals (RRIs), a total autonomic score; and enteric nervous system measured by electrogastrography (EGG). Results Significant differences were found in parasympathetic measures (RRI for HG 29.98 ± 2.95 vs. control 40.91 ± 2.38, P < 0.05); sympathetic PAR was significantly lower in patients (PAR for HG 24.5 ± 5.0 vs. 67.6 ± 11.4 for controls, P < 0.01); mean total autonomic score was significantly lower in HG (131.75 ± 9.61 vs. 196.87 ± 12.8, P < 0.05). EGG results were borderline different (normal < 3.3, HG 3.4 vs. controls 3.0, P = 0.07). Conclusion Autonomic and enteric nervous system dysfunction may play a role in the pathophysiology of HG.

Painful, swollen hands in a young woman.

A 27-year-old multigravid woman, attempting to conceive, presented with persistent pain and swelling of the knuckles and wrists for the previous 3 months. She developed difficulty opening jars and holding objects. Associated symptoms included morning joint stiffness lasting 2 hours, which improved with activity. Review of systems was negative for dry eyes and mouth, Reynaud’s symptoms, rash, photosensitivity, hair loss, chest pain, dyspnea, fever, weight loss, diarrhea, and recent viral infections or vaccinations. There was no history of conjunctivitis, urethritis, psoriasis, inflammatory bowel disease, venous thrombosis, recurrent miscarriage, or hepatitis B or C. She experienced varicella as a child and her immunization status was current. Medical history was notable for depression and migraine headaches. None of her family had inflammatory arthritis or any connective tissue disease. She worked as a clerk and did not smoke or drink alcohol. On physical examination, vital signs were as follows: temperature 96.8°F, pulse 74 beats per minute, blood pressure 132/77 mm Hg, and normal respirations. She weighed 82.1 kg (181 lbs). General appearance was normal. She had no conjunctival injection, thyromegaly, or cervical adenopathy. Cardiovascular and pulmonary examination was negative for rubs. On musculoskeletal examination, she had bilateral symmetric swelling and tenderness of the second and third metacarpophalangeal and proximal interphalangeal joints. The wrist joints were warm, tender, and painful on passive range of motion. Remaining joints were normal on examination. All fibromyalgia tender points were negative. There was no pitting edema in the legs. Laboratory studies showed a white blood cell count of 10.90 109/L (range 4–10 109/L), erythrocyte sedimentation rate of 42 mm/h (range 0–20 mm/h), C-reactive protein level of 16.3 mg/L (0–4.6 mg/L), and 25-OH vitamin D level of 10 nmol/L (80–142.5 nmol/L). Rheumatoid factor, anticyclic citrullinated peptide antibody (ACPA), antinuclear antibody, lupus anticoagulant, HLA B27, hepatitis B, hepatitis C, parvovirus antibodies, and urine pregnancy test were negative. Radiographs of the hands, including the wrists, revealed periarticular osteopenia and narrowing of the radio carpal joints. Diagnosis of seronegative rheumatoid arthritis was made in addition to hypovitaminosis D. The diagnosis of rheumatoid arthritis is based on the findings of symmetrical synovitis involving small joints of the hand, elevated inflammatory markers, and the radiologic findings. Systemic lupus erythematosus is highly unlikely in the presence of negative antinuclear antibody. The patient was counseled extensively and informed about the effect of pregnancy on rheumatoid arthritis and vice versa. The various medications that can be used during pregnancy were discussed with her. Prednisone 10 mg/d and hydroxychloroquine sulfate 200 mg twice a day were prescribed in addition to vitamin and calcium supplementation. She was referred to maternal-fetal medicine for further management.