Intrapartum management of category II fetal heart rate tracings: towards standardization of care.

There is currently no standard national approach to the management of category II fetal heart rate (FHR) patterns, yet such patterns occur in the majority of fetuses in labor. Under such circumstances, it would be difficult to demonstrate the clinical efficacy of FHR monitoring even if this technique had immense intrinsic value, since there has never been a standard hypothesis to test dealing with interpretation and management of these abnormal patterns. We present an algorithm for the management of category II FHR patterns that reflects a synthesis of available evidence and current scientific thought. Use of this algorithm represents one way for the clinician to comply with the standard of care, and may enhance our overall ability to define the benefits of intrapartum FHR monitoring.

Putting the "M" back in maternal-fetal medicine.

Although maternal death remains rare in the United States, the rate has not decreased for 3 decades. The rate of severe maternal morbidity, a more prevalent problem, is also rising. Rise in maternal age, in rates of obesity, and in cesarean deliveries as well as more pregnant women with chronic medical conditions all contribute to maternal mortality and morbidity in the United States. We believe it is the responsibility of maternal-fetal medicine (MFM) subspecialists to lead a national effort to decrease maternal mortality and morbidity. In doing so, we hope to reestablish the vital role of MFM subspecialists to take the lead in the performance and coordination of care in complicated obstetrical cases. This article will summarize our initial recommendations to enhance MFM education and training, to establish national standards to improve maternal care and management, and to address critical research gaps in maternal medicine.

Pursuit of accredited subspecialties by graduating residents in obstetrics and gynecology, 2000-2012.

OBJECTIVES: To estimate whether there has been an increase in resident graduates pursuing fellowship training in the currently accredited subspecialties and to compare whether any trend toward subspecialization is similar to those seen in other specialties. METHODS: This descriptive study examined data from the National Residency Match Program for academic years 2000-2012. Annual comparisons were made between the numbers of residents who either pursued careers in their specialty or were accepted into fellowship training in an accredited subspecialty. We compared the numbers in each group who took the American Board of Obstetrics and Gynecology (ABOG) written board examination and who became board-certified. RESULTS: Although the annual number of residency graduates in obstetrics and gynecology remained essentially the same (1,185 ± 56), the proportion of graduates accepted into fellowships increased steadily in all subspecialties (from 7.0% in 2000 to 19.5% in 2012). All other core specialties saw higher proportions of their graduates pursuing subspecialties except for family medicine. Coincident with rises in fellowship programs and positions was eventual increase in trainees who took the ABOG written examination for the first time in the three established subspecialties (maternal-fetal medicine, gynecologic oncology, reproductive endocrinology and infertility) and who became board-certified. CONCLUSION: Like with residents in other specialties, more graduates in obstetrics and gynecology are pursuing accredited subspecialty fellowship training, adding to the complexities of workforce planning. The percent of obstetrics and gynecology residents who pursued accredited subspecialty fellowship training was lower than all but one other specialty.

Randomized trial of preinduction cervical ripening: misoprostol vs oxytocin.

OBJECTIVE: The purpose of this study was to compare the vaginal delivery rate in women who undergo labor induction with preinduction misoprostol or oxytocin alone. STUDY DESIGN: Women with singleton pregnancies and Bishop scores <5 with labor induction at > or = 24 weeks of gestation were eligible; they were assigned randomly to oxytocin alone or preinduction cervical ripening with misoprostol. Labor characteristics, maternal complications, and neonatal outcomes were analyzed. RESULTS: One hundred sixty-three women received oxytocin, and 164 women received misoprostol. Maternal demographics, pretreatment Bishop scores, and labor analgesia were similar between groups. Vaginal delivery rates were also similar: 87% (n = 141) for oxytocin and 81% (n = 133) for misoprostol. Mean time from treatment to delivery was shorter for the oxytocin group, compared with the misoprostol group (13.1 vs 16.3 hours; P = .005). There was no difference in maternal complications or neonatal outcomes between groups. CONCLUSION: Preinduction cervical ripening with misoprostol did not improve the vaginal delivery rate and resulted in longer intervals to active labor and delivery. Preinduction cervical ripening with misoprostol may not be necessary.

Impact of progesterone on cytokine-stimulated nuclear factor-kappaB signaling in HeLa cells.

OBJECTIVE: A key event in the pathways leading to preterm labor may be the activation of nuclear factor-kappaB (NF-kappaB) in the fetal membranes and the cervix. Anti-inflammatory agents, such as the corticosteroids, inhibit the activation of NF-kappaB. We proposed to investigate the effects of progesterone pretreatment on cytokine-stimulated activation of NF-kappaB in HeLa cells, a human cervical epithelial cell line. METHODS: HeLa cells were pretreated with 10(-7) M progesterone for 24 hours and exposed to 1 ng/mL interleukin-1beta (IL-1beta) for 1 hour. Nuclear and cytosolic extracts were subjected to Western blot analysis using anti-p65 and anti-inhibitory protein-kappaBalpha (anti-IkappaBalpha) antibodies. Densitometric data (n=5) were compared using Kruskal-Wallis test. RESULTS: Pretreatment with progesterone interfered with IL-1beta-induced IkappaBalpha degradation. However, progesterone pretreatment resulted in a significant decrease in NF-kappaB protein subunit p65 in the cytoplasm. Pretreatment with progesterone did not reduce the amount of nuclear p65 and did not interfere with nuclear translocation of p65. CONCLUSION: Our observations suggest that any possible role played by progesterone in preterm labor prevention is not exerted through anti-inflammatory mechanisms of NF-kappaB down-regulation.

Chronic renal disease in pregnancy.

The purpose of this review was to examine the impact of varying degrees of renal insufficiency on pregnancy outcome in women with chronic renal disease. Our search of the literature did not reveal any randomized clinical trials or meta-analyses. The available information is derived from opinion, reviews, retrospective series, and limited observational series. It appears that chronic renal disease in pregnancy is uncommon, occurring in 0.03-0.12% of all pregnancies from two U.S. population-based and registry studies. Maternal complications associated with chronic renal disease include preeclampsia, worsening renal function, preterm delivery, anemia, chronic hypertension, and cesarean delivery. The live birth rate in women with chronic renal disease ranges between 64% and 98% depending on the severity of renal insufficiency and presence of hypertension. Significant proteinuria may be an indicator of underlying renal insufficiency. Management of pregnant women with underlying renal disease should ideally entail a multidisciplinary approach at a tertiary center and include a maternal-fetal medicine specialist and a nephrologist. Such women should receive counseling regarding the pregnancy outcomes in association with maternal chronic renal disease and the effect of pregnancy on renal function, especially within the ensuing 5 years postpartum. These women will require frequent visits and monitoring of renal function during pregnancy. Women whose renal disease is further complicated by hypertension should be counseled regarding the increased risk of adverse outcome and need for blood pressure control. Some antihypertensives, especially angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, should be avoided during pregnancy, if possible, because of the potential for both teratogenic (hypocalvaria) and fetal effects (renal failure, oliguria, and demise).

Physiologic changes in pregnancy and their impact on critical care.

OBJECTIVES: To describe the major pregnancy-induced physiologic changes that affect the care of patients who are critically ill. METHODS: We reviewed relevant textbooks and articles pertaining to physiologic alterations produced by pregnancy. Those changes that have a bearing on patients admitted to an intensive care unit were abstracted, summarized, and organized by organ system. CONCLUSIONS: Several organ systems manifest significant change in function during pregnancy. The cardiovascular and pulmonary systems are the two most important with regard to critical care.

Outcomes of term vaginal breech delivery.

In December 2001, the American College of Obstetricians and Gynecologists revised their recommendations for breech delivery. These recommendations acknowledge that although a planned vaginal delivery may no longer be appropriate, there are instances in which vaginal breech delivery is inevitable. Moreover, there continues to be patients who for any number of reasons will choose vaginal over cesarean delivery when faced with a fetus in the breech presentation. We sought to review maternal and fetal outcomes in such circumstances when vaginal breech delivery occurs, and compare these outcomes to elective cesarean deliveries for breech presentation. We performed a retrospective review of all singleton breech deliveries at our county hospital from January 2002 through June 2003. We reviewed maternal age, ethnicity, gestational age, gravity, parity, birthweight, mode of delivery, Apgar scores, umbilical arterial blood gases, and maternal and infant complications of both cesarean deliveries and vaginal breech deliveries. Univariate and logistic regression statistical analyses were performed with NCSS software. We had a total of 150 term breech deliveries with gestational ages between 37 and 42 weeks. Of these, 41 were vaginal breech and 109 were cesarean deliveries. Greater than 95% of patients are of Hispanic origin. There were no statistically significant differences in maternal age, ethnicity, gravity, or gestational age. Mean birthweight was significantly lower and parity was significantly higher in the vaginal delivery group. There was also a higher proportion of patients who underwent labor induction/augmentation in the vaginal group. We found no differences in the outcomes of 5-minute Apgar scores, umbilical arterial blood gas values, neonatal intensive care unit admissions, deaths or maternal/fetal complications reported between the two groups. Mean umbilical arterial blood gas values were greater than 7.18 in both groups. Vaginal breech delivery cannot always be avoided. Moreover, at our county hospital several patients continue to choose vaginal breech delivery. Our data would suggest that vaginal breech delivery remains a viable option in selected patients.

Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human mesangial cells and induce interleukin-6 and plasminogen activator inhibitor-1 secretion.

BACKGROUND: Preeclampsia affects 3-5% of all pregnancies. It is a major cause of maternal and fetal morbidity and mortality. Recent studies demonstrate that autoantibodies against the angiotensin II type 1 (AT(1)) receptor are present in the serum of preeclamptic patients. In this study, we investigated the role of AT(1) receptor-agonistic autoantibody (AT1-AA) regarding interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (Pai-1) secretion in human mesangial cells. METHODS: The study included ten patients: five severely preeclamptic and five normotensive pregnant women. Immunoglobulin-G (IgG) was purified from each individual. The presence of AT1-AA was determined based on its ability to stimulate an increase in the contraction rate of rat neonatal cardiomyocytes. Primary human mesangial cells were chosen to study IgG-induced secretion of IL-6 and Pai-1. Losartan and epitope peptides were used to determine whether AT1-AA interaction with AT(1) receptor was associated with stimulation of IL-6 and Pai-1 secretion and was mediated through AT(1) receptor activation. RESULTS: The IgG from preeclamptic patients stimulated an increased contraction rate in rat neonatal cardiomyocytes. The IgG from preeclamptic patients induced the AT(1) receptor-specific secretion of IL-6 and Pai-1 from human mesangial cells at a significantly higher level than that achieved with IgG from normotensive patients. Competition with an epitope peptide suggested that the AT(1) receptor was stimulated by AT1-AA. CONCLUSIONS: Our findings suggest that a maternal autoantibody with the ability to activate AT(1) receptors may account for the development of renal damage seen in preeclamptic patients.

Effects of nuchal cord on birthweight and immediate neonatal outcomes.

Our objective was to ascertain if nuchal cord is associated with adverse neonatal outcomes. Using a retrospective database of term neonates, outcomes were compared among infants with 0, 1, and 2 or more loops of cord encircling the neck. Of 4426 neonates, 3651 served as controls, 691 had one loop, and 84 had two or more loops. There were no significant differences in the mean birthweight, the frequency of nonreassuring fetal heart rate patterns, operative vaginal deliveries, or 5-minute Apgar scores of < 7. The cesarean delivery rate was significantly different among the three groups and was the highest among the group of women whose fetus had no nuchal cord ( p < 0.01). A nuchal cord at term is not associated with untoward pregnancy outcomes.

Characterization of corticosteroid redosing in an in vitro cell line model.

OBJECTIVE: The purpose of this study was to investigate dexamethasone redosing as function of time and dose. STUDY DESIGN: We studied the effect of 48 hours' exposure to various concentrations of dexamethasone in a human pulmonary adenocarcinoma cell line (H-441). We measured the level of surfactant protein B (SP-B) mRNA by quantitative reverse transcription-PCR after initial dexamethasone exposure, and after redosing, 1 or 2 weeks later. Values are mean +/- SE for 5 experiments. Comparisons were made by Mann-Whitney and Kruskal-Wallis test with significance set at P < .05. RESULTS: Induction of SP-B mRNA was maximal within 48 hours of the initial dexamethasone exposure. Redosing with the same dexamethasone concentration resulted in levels more than double those initially observed. Redosing with dexamethasone concentration 10 times lower had an effect comparable to that of the initial, higher concentration. CONCLUSION: Our results suggest a residual effect of the initial exposure that potentiates redosing, allowing significant dose reductions.

T helper cell cytokine profiles in preterm labor.

PROBLEM: To compare concentrations of T-helper cell cytokines in women with preterm labor (PTL) to normal pregnancies. METHOD OF STUDY: Fourteen women with PTL and 13 women with normal pregnancies from 24 to 34 weeks were enrolled in this pilot study. Peripheral blood mononuclear cells (PBMCs) and cervical secretions were collected. PBMCs were cultured and stimulated with mitogens. Culture supernatants and cervical secretions were assayed for type 1 (interferon-gamma, IL-12) and type 2 cytokines (IL-4, IL-5, IL-10 and IL-13) using enzyme-linked immunosorbent assays. RESULTS: There were no intergroup differences in median cytokine concentrations in PBMC cultures, or in ratios of type 1/type 2 cytokines. In cervical secretions, the median concentration of IL-4 was significantly higher in control patients. CONCLUSIONS: PTL patients appeared to have an altered T-helper cytokine balance in cervical secretions. Further study of the role of cytokines produced in the adaptive response appears warranted.

Antibodies from preeclamptic patients stimulate increased intracellular Ca2+ mobilization through angiotensin receptor activation.

BACKGROUND: Preeclampsia is a serious disorder of pregnancy characterized by hypertension, proteinuria, edema, and coagulation and vascular abnormalities. At the cellular level, abnormalities include increased calcium concentration in platelets, lymphocytes, and erythrocytes. Recent studies have shown that antibodies directed against angiotensin II type I (AT1) receptors are also highly associated with preeclampsia. METHODS AND RESULTS: We tested the hypothesis that AT1 receptor-agonistic antibodies (AT1-AAs) could activate AT1 receptors, leading to an increased intracellular concentration of free calcium and to downstream activation of Ca2+ signaling pathways. Sera of 30 pregnant patients, 16 diagnosed with severe preeclampsia and 14 normotensive, were examined for the presence of IgG capable of stimulating intracellular Ca2+ mobilization. IgG from all preeclamptic patients activated AT1 receptors and increased intracellular free calcium. In contrast, none of the normotensive individuals had IgG capable of activating AT1 receptors. The specific mobilization of intracellular Ca2+ by AT1-AAs was blocked by losartan, an AT1 receptor antagonist, and by a 7-amino-acid peptide that corresponds to a portion of the second extracellular loop of the AT1 receptor. In addition, we have shown that AT1-AA-stimulated mobilization of intracellular Ca2+ results in the activation of the transcription factor, nuclear factor of activated T cells. CONCLUSIONS: These results suggest that maternal antibodies capable of activating AT1 receptors are likely to account for increased intracellular free Ca2+ concentrations and changes in gene expression associated with preeclampsia.

The effects of dexamethasone and betamethasone on surfactant protein-B messenger RNA expression in human type II pneumocytes and human lung adenocarcinoma cells.

OBJECTIVE: The purpose of this study was to compare the effect of a single 48-hour exposure to betamethasone or dexamethasone in the NCI-H441 cell line and in human type II pneumocytes. STUDY DESIGN: NCI-H441 cells were exposed 48 hours to varying concentrations of betamethasone or dexamethasone (10(-10) to 10(-7) mol/L) alone or in combination with 1 mmol/L dibutyryl cyclic adenosine monophosphate. Likewise, human type II pneumocytes were exposed 48 hours to varying concentrations of betamethasone or dexamethasone (10(-9) to 10(-7) mol/L) alone or in combination with 1 mmol/L dibutyryl cyclic adenosine monophosphate. The measured outcome was the stimulatory effect on surfactant protein B gene transcription as expressed by surfactant protein B messenger RNA accumulation. The experiment was conducted 5 times in NCI-H441 cells and 6 times in type II cells, in parallel with control. Surfactant protein B messenger RNA was determined at control level and 48 hours after exposure by quantitative reverse transcription-polymerase chain reaction. RESULTS: A similar dose-dependent response in surfactant protein B messenger RNA expression was seen with both betamethasone and dexamethasone. In human type II pneumocytes, the inductive profile of surfactant protein B messenger RNA after 48-hour exposure to betamethasone or dexamethasone was similar to that seen in the NCI-H441 cells. CONCLUSION: Dexamethasone and betamethasone achieved similar dose-response patterns of surfactant protein-B expression in vitro.

Antenatal corticosteroids for fetal maturation in women at risk for preterm delivery.

The available data unambiguously support the beneficial, short-term fetal effects of antenatal corticosteroids in women at risk for preterm delivery. There are still several incompletely addressed questions, including the use of corticosteroids in women with preterm premature rupture of membranes, the optimal corticosteroid preparation to be used, and the impact of repeated dosing. These issues are discussed in this review from the perspective of recent scientific evidence on the mechanisms responsible for positive short-term effects on survival and possible harmful long-term effects.

Mirror syndrome. A case report.

BACKGROUND: Water retention in a pregnant woman can mirror fetal hydropic changes. This clinical presentation has been named "mirror syndrome." Awareness of the syndrome is important due to the associated fetal and maternal risks. CASE: A 26-year-old woman, gravida 3, para 1011, presented at 31 weeks' gestation with significant edema and a 7-km weight gain in one week. Sonographic evaluation revealed hydramnios and fetal ascites. Maternal workup was negative for preeclampsia, diabetes, or cardiac or renal dysfunction. A workup for nonimmune hydrops was also negative. Over the next three days there was progression of maternal edema. With diagnosis of mirror syndrome, the decision for delivery was made. Both neonate and mother subsequently did well, with normalization of ascites and edema, respectively. CONCLUSION: Our case, along with 19 reviewed in the literature, reiterate the features of mirror syndrome and provide an opportunity to dispel some of the misconceptions in the literature. The condition is frequently mistaken for preeclampsia, although distinguishing characteristics can be identified. Mirror syndrome is a manifestation of extremely severe fetal hydrops. When the specific cause of fetal hydrops cannot be identified and corrected, immediate delivery is necessary in order to avoid fetal death and maternal complications.