Factors influencing preconception control of glycemia in diabetic women.

BACKGROUND: Although periconceptional glycemic control directly impacts perinatal outcome for pregestational diabetic women, these women still frequently enter pregnancy with suboptimal control of glycemia. OBJECTIVES: To determine how frequently diabetic women enter pregnancy with suboptimal glycemic control and to identify factors associated with not achieving optimal periconceptual control of glycemia. PATIENTS AND METHODS: Pregestational diabetic women (n = 55) who attended the Maternal Fetal Medicine Faculty Practice or the Resident Medical Complications Obstetric Clinic, Magee Women's Hospital, Pittsburgh, Pa, were administered a brief questionnaire pertaining to periconceptional education and control of glycemia. Levels of periconceptional hemoglobin A1c, were measured in all patients. RESULTS: Sixty-one percent of pregestational diabetic women presented for prenatal care with suboptimal control of their blood glucose levels (hemoglobin A1c measurement, >0.08). Of the 55 diabetic women who participated in the questionnaire, 47 (86%) were under the care of a physician for their diabetes, 45 (82%) monitored their glucose level at least 3 times per day, 34 (60%) stated that they had been advised to plan a pregnancy, and 29 (53%) stated that they had planned their pregnancies. Women who had not been advised to achieve target hemoglobin A1c levels were more likely to enter pregnancy with suboptimal control of their blood glucose levels (P = .02). Women who experienced prior complications with pregnancy were significantly more likely to enter pregnancy with suboptimal control of their blood glucose levels (P = .02). CONCLUSIONS: Diabetic women frequently enter pregnancy with suboptimal control of glycemia. Women not advised to achieve target glucose or hemoglobin A1c levels were more likely to enter pregnancy with suboptimal control of glycemia.

Association of pregnancy complications and choice of immunosuppressant in liver transplant patients.

BACKGROUND: The purpose of this study was to identify factors associated with antenatal complications for an ongoing series of pregnant women who have undergone orthotopic liver transplantation. METHODS: We reviewed Magee-Womens Hospital records from 14 pregnancies in 13 women in whom a liver had been transplanted before pregnancy. We collected and analyzed data regarding the primary liver disease, allograft status, liver function at conception and during pregnancy, immunosuppressive medications, associated medical conditions, time from transplant to conception, cytomegalovirus serostatus, and maternal and fetal outcome. RESULTS: Seven patients had evidence of renal dysfunction (creatinine, 1.3-2.0 mg/dl), five of whom also were hypertensive at their first prenatal visit. The complications of preeclampsia, worsening hypertension, and small for gestational age occurred only in women with renal dysfunction at conception. Renal dysfunction was more often associated with cyclosporine than tacrolimus use. CONCLUSIONS: Renal dysfunction is the primary determinant of adverse pregnancy outcome in liver transplant recipients. Immunosuppression with cyclosporine during pregnancy was more often associated with antenatal complications than with the use of tacrolimus.

Reproductive function and outcome of pregnancy after liver transplantation in women.

OBJECTIVE: To discuss menstrual function before and after liver transplantation, immunosuppression during pregnancy, outcome and management of pregnancy, and use of contraception in women after liver transplantation. MATERIAL AND METHODS: We review the relevant medical literature and describe our clinical experience in the management of gynecologic and obstetric issues in recipients of liver transplants. RESULTS: Menstrual abnormalities, such as amenorrhea, oligomenorrhea, irregular bleeding, and metrorrhagia, are common in women with liver disease and may often be the first clinical indication of liver dysfunction. Normal menstrual function is frequently restored after transplantation. Successful pregnancies have occurred in recipients of liver transplants, but such pregnancies are often complicated by preterm delivery, preeclampsia, and infection. Use of immunosuppressive medications should be maintained during pregnancy, and drug concentrations should be carefully monitored; none has been found to be teratogenic. Pregnancy does not seem to accelerate graft rejection. Barrier contraception or sterilization, if appropriate, seems to be the safest option for these patients. CONCLUSION: Because liver transplantation leads to restoration of normal menstruation, female patients of reproductive age must be counseled about the possibility of pregnancy and the use of contraception. Pregnancy should be avoided for at least the first 6 months after transplantation. With specialized care and attention, pregnancies are generally associated with good outcomes.

The prostaglandin synthesis inhibitor ketorolac blocks ritodrine-stimulated production of prostaglandin F2 alpha in pregnant sheep.

OBJECTIVE: To determine whether ritodrine-stimulated production of prostaglandin (PG) F2 alpha by pregnant uterine tissues can be blocked by the concurrent administration of ketorolac, a PG synthesis inhibitor. METHODS: We infused saline, ritodrine, ketorolac, or a combination of ritodrine and ketorolac into chronically catheterized pregnant sheep. Concentrations of PGF2 alpha in uterine venous plasma were measured by radioimmunoassay at 0, 1, 2, 3, 4, and 24 hours during the infusions. RESULTS: Ritodrine significantly increased uterine venous PGF2 alpha; mean percent increases at 4 hours were 330% and 380%, and at 24 hours 370%, compared with controls. During concurrent ritodrine and ketorolac infusion, there was no increase in uterine venous PGF2 alpha at any time. CONCLUSIONS: Ketorolac completely blocks ritodrine-stimulated production of PGF2 alpha in pregnant uterine tissues. We conclude that ritodrine stimulates PG production through mobilization of arachidonic acid, and this can be effectively blocked with a PG synthesis inhibitor. This finding may have important clinical applications in the treatment of preterm labor.

Hemorrhagic complication of anticoagulation during pregnancy in a woman with lupus anticoagulant.

BACKGROUND: Lupus anticoagulant is an acquired antiphospholipid antibody that can increase greatly the risk of thromboembolism during pregnancy. Because a baseline elevated activated partial thromboplastin time (PTT) is associated frequently with this antibody, monitoring anticoagulant effect with activated PTT can be unreliable. CASE: A pregnant woman with lupus anticoagulant being treated with adjusted dose heparin experienced concurrent severe thrombotic and hemorrhagic complications. CONCLUSION: This case illustrates the pitfall of activated PTT monitoring when administering anticoagulation therapy to a patient with a baseline elevated activated PTT. We propose that heparin levels be used to monitor anticoagulation in these patients.

Peak expiratory flow rate in normal pregnancy.

OBJECTIVE: To determine whether peak expiratory flow rate changes with pregnancy and advancing gestation. METHODS: We measured the peak expiratory flow rate in 57 women during each trimester of pregnancy and postpartum. During four visits, all subjects exhaled forcefully three times into a peak flow meter. For each visit, the best of three attempts defined their peak expiratory flow rate. Using accepted standard nomograms, we normalized peak expiratory flow rate with respect to height and age. Using analysis of variance, we compared the mean normalized peak expiratory flow rates in each of the trimesters and postpartum. RESULTS: The subjects' peak expiratory flow rates did not change significantly during the three trimesters and postpartum (P = .317). The mean peak expiratory flow rates for the three trimesters and postpartum were 434 +/- 18, 452 +/- 16, 444 +/- 15, and 450 +/- 16 (values in liters per minute +/- 95% confidence intervals [CIs]). The mean normalized peak expiratory flow rates for the three trimesters and postpartum were 0.92 +/- 0.036, 0.95 +/- 0.032, 0.94 +/- 0.030, and 0.95 +/- 0.031 (values +/- 95% CI). CONCLUSIONS: This study demonstrates that peak expiratory flow rate does not change with pregnancy and advancing gestation. Therefore, testing peak expiratory flow rate in pregnancy is valid, and physicians can use peak expiratory flow rate accurately and reliably in the management of pregnant women with asthma.

Changes in uterine venous prostaglandin F metabolites following intravenous infusion of ritodrine in sheep.

The effectiveness of the beta-adrenergic receptor agonist ritodrine as a tocolytic agent is limited by the tachyphylaxis that occurs with its sustained usage. In order to understand the nature of this tachyphylaxis, we investigated the effect of ritodrine on uteroplacental prostaglandin (PG)F2 alpha production in pregnant sheep. Using general anesthesia in five pregnant sheep, we placed catheters in the aorta and vena cava and in the uterine vein from the uterine horn. In random order on different days, we infused ritodrine (4 micrograms/kg/minute) or physiologic saline into the maternal vena cava at a rate of 0.184 mL/minute. Uterine venous and maternal arterial blood was sampled 60 minutes before and immediately before the infusion and then at 60, 120, 180, and 240 minutes during the infusion. After centrifugation, the serum was frozen and then assayed for the metabolite of PGF2 alpha (PGFM). Uterine venous PGFM increased significantly after 60 minutes of ritodrine infusion (mean increase 1.164 ng/mL; P less than .05), and this increase was sustained during the 4-hour infusion. The PGFM gradient across the uteroplacental bed (uterine vein - aorta) was also significantly elevated during the infusion, suggesting a uteroplacental or fetal membrane source of the PG. Saline had no effect on uterine venous PGFM or the PGFM gradient. These results suggest that ritodrine stimulates PGF2 alpha production, and this may contribute to the tachyphylaxis that occurs with ritodrine and limits its long-term effectiveness as a tocolytic agent.

Rapid assessment of fetal hemoglobin concentration with the HemoCue system.

Successful treatment of severe fetal hemolytic disease depends on rapid and accurate measurement of fetal hemoglobin or hematocrit. The HemoCue is a portable hemoglobinometer that rapidly measures hemoglobin concentration. To evaluate the potential role of this instrument in fetal transfusion therapy, we measured hemoglobin concentration with the HemoCue and compared it with Coulter counter determination of hemoglobin in 39 fetuses. The HemoCue accurately measured fetal hemoglobin concentration (y = -0.3986 + 1.0276x; r = 0.97, P less than .001). This instrument is valuable for use with intravascular fetal transfusions.

Transvesical cesarean following bowel and urinary tract reconstructive surgery.

Intentional transvesical cesarean was done for delivery in a woman born with an imperforate anus, ectopic intravaginal urethra, and vaginal and urethral strictures. She had undergone multiple reconstructive procedures that left her bladder completely covering the anterior uterine surface. The rest of the uterus, including the fundus and the broad ligaments, was obscured by multiple bowel adhesions. Cesarean delivery was necessary because of pelvic bone and soft-tissue deformity. Anterior and posterior vertical cystotomies resulted in exposure of the anterior uterine wall, and the fetus was delivered through a vertical uterine incision. The woman recovered and 6 months later has no genitourinary complaints.

Erythropoietin in pregnancies complicated by severe anemia of renal failure.

BACKGROUND: Recombinant human erythropoietin has been approved for treatment of the anemia of renal failure since 1989, yet data regarding the safety and efficacy of this drug in pregnancy are limited. We used recombinant human erythropoietin to treat the anemia of renal disease in three pregnant women. CASES: Nadir hematocrit values before initiation of erythropoietin were 19-23%. Erythropoietin, 50-160 U/kg/week subcutaneously, was begun at 14-26 weeks' gestation. Initially, the rise in hematocrit averaged 0.6-2% each week, with peak values of 26.7-32%. Iron supplementation was given simultaneously. Maternal and neonatal outcomes were favorable despite the development of preeclampsia or worsening renal function requiring early delivery. CONCLUSION: In this small series, erythropoietin begun during the second trimester in a dose of about 100 U/kg/week, in conjunction with orally administered iron, appeared to be effective in treating the anemia of renal failure during pregnancy. Additional experience is needed to evaluate the safety of this medication during pregnancy.

Pregnancy and liver transplantation.

To define the risks and outcomes associated with pregnancy and liver transplantation, we reviewed our experience in managing eight pregnant women who had undergone orthotopic liver transplantation. Seven patients conceived after transplantation; the interval from transplantation to conception ranged from 3 weeks to 24 months. One patient received an allograft at 26 weeks' gestation for hepatic failure secondary to acute fulminant hepatitis B. Of the seven patients who conceived after transplantation, six had live births and one electively terminated her pregnancy. Five patients developed worsening hypertension and/or preeclampsia. Three patients developed severe preeclampsia and required delivery. One patient suffered acute allograft rejection during pregnancy which was successfully treated with corticosteroids. Two patients had persistent elevation of serum transaminases and two had severe anemia. The mean gestational age at delivery was 32.8 weeks. Of the six live births to women who conceived after transplantation, five infants survived and are well and one infant died. There were no congenital anomalies. All mothers are alive at this time. Pregnancy in recipients of hepatic allografts is associated with good perinatal outcome, but there is an increased risk of preeclampsia, worsening hypertension, and preterm delivery. Pregnancy does not appear to have a deleterious effect on hepatic graft function or survival. Joint management of these patients by a transplant specialist and a perinatologist is essential.

Magnetic resonance imaging to diagnose a müllerian anomaly during pregnancy.

An adolescent woman presented with a paravaginal mass during pregnancy. Magnetic resonance imaging was useful in diagnosing a müllerian anomaly consisting of a double uterus and cervix and blind vaginal pouch. Magnetic resonance imaging can be an important modality in the diagnosis of gynecologic conditions in the obstetric patient.

A sonographic and karyotypic study of second-trimester fetal choroid plexus cysts.

A prospective study was undertaken of 513 women between 15.6-24.1 weeks' gestation who had a level II ultrasound examination followed immediately by a genetic amniocentesis. The presence or absence of fetal choroid plexus cysts was noted and the results correlated with the fetal karyotype. Thirteen cases of choroid plexus cysts were observed sonographically, a prevalence of 2.5%. The size of the cysts ranged from 3-10 mm, with a median of 6 mm. There were no other sonographically detectable congenital abnormalities in these 13 cases, and the fetal karyotype was normal in all. An association between fetal choroid plexus cysts and autosomal trisomies was not found in this series.

Pregnancy after liver transplantation.

This article reviews the reported experience with pregnancy after liver transplantation and describes obstetric risks and medical issues that the maternal fetal medicine specialist has a reference for managing these pregnancies and for providing appropriate preconception counseling. Women who undergo liver transplantations have a higher risk of preeclampsia, worsening hypertension, preterm premature rupture of membranes, anemia, small for gestational age, preterm delivery, and cesarean section than the normal obstetric population. Women with preconceptional renal dysfunction appear to be at greatest risk for pregnancy complications. Women who conceived within 6 months of transplant had a high risk of rejection. Reproductive-aged recipients of liver allograft should receive contraception and preconception counseling. In an appropriately timed and planned pregnancy, women who undergo liver transplantations can have successful pregnancies with little risk to their allograft function.

Pregnancy outcomes in a prospective matched control study of pregnancy and renal disease.

OBJECTIVE: Assessment and comparison of pregnancy outcomes in women with renal disease and women with high risk pregnancies due to medical illness without renal disease. DESIGN: A prospective, matched controlled study. SETTING: The High Risk Obstetrical Clinics of Magee Women's Hospital, a primary and referral center where approximately 9,500 deliveries occur per year. PATIENTS: Two groups of pregnant women, all identified in the first trimester. The study group included 43 pregnancies in 40 women with renal disease as defined by: 1) known renal disease antedating pregnancy, 2) prepregnant proteinuria > or = 150 mg/24 hours, or 3) first trimester serum creatinine > or = 0.8 mg/dl or proteinuria > or = 300 mg/24 hours. The 43 controls included women with medical problems other than renal disease that placed them at high obstetrical risk. Control women were matched to study women for parity, advanced maternal age, race, and insulin-dependent diabetes mellitus. MEASUREMENTS: For all patients, blood pressure was recorded once at approximately 10, 20, and 30 weeks gestation. For study patients, serum creatinine, 24-hour urinary protein, and creatinine clearance were obtained at least once in each trimester. Pregnancy outcomes were recorded as favorable if gestation was > or = 36 weeks and without evidence of intrauterine growth retardation. Adverse pregnancy outcomes included prematurity, intrauterine growth retardation, intrauterine fetal death, spontaneous abortion, or neonatal death. RESULTS: Forty-two percent of study and control patients were diabetic. First trimester renal function was normal (creatinine < 0.8 mg/dl) in 12 study patients, mildly impaired in 24 (creatinine 0.8-1.4 mg/dl) and moderately impaired in 5 (creatinine > or = 1.4 mg/dl). Compared with controls, first and third trimester hypertension was more prevalent in the study patients (p = 0.003, p = 0.012); overall mean blood pressure was also higher in study patients (92 +/- 11 mmHg vs 85 +/- 8 mmHg, p = 0.002). The mean gestational age was shorter in the study patients (33.4 +/- 6.9 weeks vs 37.2 +/- 4 weeks, p = 0.001). Overall pregnancy loss was more common in the study patients (14/43 vs 3/43, p = 0.003) with spontaneous abortion contributing half of those pregnancy losses (7/14). Hypertension in any trimester was associated with adverse pregnancy outcome in study but not control patients. In the subset of study patients, adverse fetal outcome was directly associated with degree of renal dysfunction and proteinuria. CONCLUSIONS: Pregnancy outcome in women with renal disease was significantly worse than in the control group and showed no improvement over retrospective reports from the 1970's and 1980's. Specifically, fetal deaths were more common in women with renal disease and were predicted by proteinuria and the degree of renal dysfunction. The uncommonly low number of spontaneous abortions in the control group may have contributed to the worse fetal outcome in the study patients compared with controls. Women with diabetes mellitus and hypertension are at particularly high risk for relatively poor pregnancy outcome. These higher risks should be discussed when counseling women with renal disease who contemplate pregnancy.

Low-dose aspirin and prednisone treatment of pregnancy loss caused by lupus anticoagulants.

The objective of this study was to ascertain the complications and the efficacy of low-dose aspirin (LDA) and prednisone therapy in women with pregnancy loss and "lupus anticoagulants" (LAC). During the period 1985 to 1993, 255 patients with two or more pregnancy losses (RPL) were tested for LAC with an activated partial thromboplastin time (aPTT) and a tissue thromboplastin inhibition index (TTI, normal value < 1.3). The diagnosis of LAC was established if two TTI values were > or = 1.3 or if a prolonged aPTT was measured in the patient's plasma that did not correct to normal by 1:1 mixing with normal plasma. We excluded patients with RPL who had only anticardiolipin antibodies. We treated 28 pregnancies in 21 women with LDA/prednisone for RPL associated with LAC. Therapy with LDA/prednisone was initiated as soon as a viable pregnancy was diagnosed. Therapy was continued until delivery in all but one case. Prednisone dose was minimized by measuring TTI and aPTT every 2 weeks and adjusting the dosage to maintain a TTI < or = 1.2 and to correct the aPTT to less than 36 seconds. Among the 28 pregnancies there were four (14%) first-trimester spontaneous abortions and four (14%) second-trimester fetal deaths. Of 20 surviving neonates (72%), seven were delivered after 37 weeks and 13 before 37 weeks (mean 35.9 +/- 2.3 weeks, range 31.5 to 40.4 weeks). Pre-term premature rupture of membranes occurred in three pregnancies, hypertensive disorders in six, and four small-for-gestational-age neonates were delivered (two stillborn). Mean birth weight of 20 surviving neonates was 2736 +/- 763 gm (range 900 to 3920 gm). Mean daily prednisone dose in 20 live births was 24.1 +/- 8.5 (SD) mg (range 11.3 to 49.3 mg/day) with mean duration of LDA/prednisone therapy of 185 +/- 40 days (range 97 to 223 days). Maximum prednisone dose was 60 mg/day (mean 36.8 +/- 12.7 mg/day). Only one serious maternal complication of LDA/prednisone therapy was observed. One neonate had talipes equinovarus that resolved without surgical therapy. LDA/prednisone therapy seemed effective and reasonably well tolerated in this population. These findings should be confirmed in a prospective, controlled investigation if such a trial can be organized and performed.

Indicated preterm birth: a possible contribution to group B streptococcal sepsis prophylaxis protocol failures. A case report.

BACKGROUND: Despite the acceptance of protocols for the prevention of group B streptococcal (GBS) sepsis for the newborn, protocol violations, with subsequent failure to initiate intrapartum antibiotic therapy, occur at many institutions. The causes for GBS prophylaxis protocol violations are not well understood. CASES: We report two cases of indicated preterm birth in which appropriate antibiotic prophylaxis for GBS sepsis was not initiated. CONCLUSION: In the setting of indicated preterm birth, GBS prophylaxis may be overlooked. We suspect that the attention given to the medical or fetal complications of indicated preterm birth may contribute to the omission of GBS sepsis prophylaxis in these situations.

Unusual presentations of fetal teratoma.

Teratomas are the most common congenital neoplasm. Fetal intracranial teratomas generally are large solid/cystic tumors that often completely replace normal brain tissue. Mediastinal teratomas are uncommon and rarely result in nonimmune hydrops fetalis. We describe two unusual presentations of fetal teratoma. The first is a fetus with massive hydrocephalus and marked facial deformities that were caused by a small intracranial teratoma. The second is a fetus with a mediastinal teratoma associated with non-immune hydrops fetalis. In both cases, compression by the mass resulted in lethal sequelae.

First-trimester pancreatitis. Maternal and neonatal outcome.

OBJECTIVE: To determine the incidence and maternal-fetal outcome of first-trimester pancreatitis at one institution. STUDY DESIGN: A retrospective study of pancreatitis presenting during the first trimester of pregnancy over a 10-year period at Magee Womens Hospital. RESULTS: There were 11 cases, for an incidence of 0.1/1,000 live births. There was no maternal mortality. Three patients elected voluntary termination, and eight pregnancies proceeded to term. All delivered at > or = 35 weeks. The mean gestational age was 38.9 +/- 2.1 weeks (mean +/- SD), and mean birth weight was 3,103 +/- 641 g. There were no adverse neonatal outcomes, although one patient had a fetus with severe intrauterine growth retardation. Maternal morbidity and complications were due mainly to gallstone pancreatitis, which was the most commonly identified cause of pancreatitis, and three patients underwent cholecystectomy during pregnancy or the puerperium. No first-trimester pregnancy terminations were performed for medical indications. Pancreatitis tended to recur during the examined pregnancy (mean number of admissions, 2.27 +/- 2.1). CONCLUSION: Patients should be advised of the relapsing nature of pancreatitis that presents during the first trimester. However, there is a good prognosis for pregnancy outcome.

Successful pregnancy after bilateral hypogastric artery ligation. A case report.

BACKGROUND: Selective embolization of the hypogastric arteries is an effective, nonsurgical alternative for the management of obstetric and gynecologic hemorrhage. Successful pregnancy following bilateral hypogastric artery occlusion has been reported, but experience is extremely limited. CASE: We report a case of successful pregnancy in a patient previously treated with bilateral hypogastric artery embolization. Although a diminution of fetal growth toward term was observed, the fetus tolerated labor and subsequently thrived, without sequelae. CONCLUSION: This case supports the possibility of normal labor for women who conceive after bilateral hypogastric artery embolization.