An evaluation of fetal heart rate characteristics associated with neonatal encephalopathy: a case-control study.

OBJECTIVE: We sought to identify fetal heart rate (FHR) characteristics that are associated with neonatal encephalopathy (NE). DESIGN: Retrospective case-control study. SETTING: A single medical centre in Shanghai, China, 2006-2015. SAMPLE: Women delivering a singleton, non-anomalous infant at ≥36 weeks' gestation diagnosed with NE (cases, n = 109) were compared with a group of women with unaffected infants (controls, n = 233). METHODS: Two physicians blinded to the outcome independently reviewed FHR tracings during the last 30 minutes of tracing prior to delivery. FHR characteristics were compared in the two groups and multivariable logistic regression was used to adjust for confounding. MAIN OUTCOME MEASURES: Adjusted odds ratio (aOR) and 95% confidence interval (CI) for the presence of specific FHR categories and characteristics. RESULTS: Category II FHR tracings were observed in 89% of women prior to delivery and were not independently associated with NE. Notably, a category III FHR was observed in 17.4% of women in the NE group compared with 0.9% of women in the control group (aOR 44.99, 95% CI 7.23-279.97). Bradycardia, minimal/absent variability, late decelerations and prolonged decelerations were independently associated with NE, whereas accelerations were protective. Similar findings were found when the cases were limited to NE with arterial cord pH <7.1 and in a subgroup analysis of women with category II tracings. CONCLUSIONS: Category III tracings, while infrequent, are not uncommon prior to delivery among fetuses who develop NE. In contrast, most FHR tracings are category II prior to delivery; however, individual FHR characteristics within this category are associated with NE. FUNDING: This research was supported by the Interdisciplinary Programme of Shanghai Jiao Tong University. TWEETABLE ABSTRACT: Category III tracings are not uncommon prior to delivery among fetuses who develop neonatal encephalopathy.

Prenatal vitamin C and E supplementation in smokers is associated with reduced placental abruption and preterm birth: a secondary analysis.

OBJECTIVE: Smoking and pre-eclampsia (PE) are associated with increases in preterm birth, placental abruption and low birthweight. We evaluated the relationship between prenatal vitamin C and E (C/E) supplementation and perinatal outcomes by maternal self-reported smoking status focusing on outcomes known to be impacted by maternal smoking. DESIGN/SETTING/POPULATION: A secondary analysis of a multi-centre trial of vitamin C/E supplementation starting at 9-16 weeks in low-risk nulliparous women with singleton gestations. METHODS: We examined the effect of vitamin C/E by smoking status at randomisation using the Breslow-Day test for interaction. MAIN OUTCOME MEASURES: The trial's primary outcomes were PE and a composite outcome of pregnancy-associated hypertension (PAH) with serious adverse outcomes. Perinatal outcomes included preterm birth and abruption. RESULTS: There were no differences in baseline characteristics within subgroups (smokers versus nonsmokers) by vitamin supplementation status. The effect of prenatal vitamin C/E on the risk of PE (P = 0.66) or PAH composite outcome (P = 0.86) did not differ by smoking status. Vitamin C/E was protective for placental abruption in smokers (relative risk [RR] 0.09; 95% CI 0.00-0.87], but not in nonsmokers (RR 0.92; 95% CI 0.52-1.62) (P = 0.01), and for preterm birth in smokers (RR 0.76; 95% CI 0.58-0.99) but not in nonsmokers (RR 1.03; 95% CI 0.90-1.17) (P = 0.046). CONCLUSION: In this cohort of women, smoking was not associated with a reduction in PE or the composite outcome of PAH. Vitamin C/E supplementation appears to be associated with a reduction in placental abruption and preterm birth among smokers.

Clinical and cardiovascular magnetic resonance profile of cardiomyopathy patients from South Africa: Pilot of the IMHOTEP study.

BACKGROUND: Cardiomyopathy is an important cause of heart failure, however, there is notable lack of data on causes and manifestations of cardiomyopathy in Africa. AIMS: The African Cardiomyopathy and Myocarditis Registry Program (IMHOTEP) aims to address the knowledge gap on etiology, treatment, and outcomes of cardiomyopathy in sub-Saharan Africa. METHODS AND RESULTS: We conducted a single-center pilot study to delineate the clinical and cardiovascular magnetic resonance (CMR) phenotypes of cardiomyopathy in South African patients. Assessment of the first 99 adult incident cases [mean age 36.8 ± 12.5 years; females 53.5%] enrolled in IMHOTEP showed that dilated cardiomyopathy (n = 77) was commonest, followed by hypertrophic (n = 13), restrictive (n = 5) and arrhythmogenic (n = 4) cardiomyopathies. A broad range of etiologies were encountered with secondary causes identified in 42% of patients. Onset of symptoms in the peripartum period was observed in 47% of women, and peripartum cardiomyopathy was diagnosed in 32.1% of women recruited. In addition to electrocardiography and echocardiography, CMR was performed in 67 cases and contributed diagnostically in a third of cases. Acute inflammation was rarely observed [2%] on CMR, however, late gadolinium enhancement (LGE) was noted in 92% of cases. CONCLUSION: We report a diverse spectrum of causes of cardiomyopathy in the South African population, with secondary, potentially treatable, etiologies in a significant proportion of cases. CMR was useful in delineating specific phenotypes and etiologies, influencing clinical care. A higher-than-expected burden of LGE was observed in this young patient cohort - the implications of which are yet to be determined.

Evaluation of in vivo T cell kinetics: use of heavy isotope labelling in type 1 diabetes.

CD4(+) memory cell development is dependent upon T cell receptor (TCR) signal strength, antigen dose and the cytokine milieu, all of which are altered in type 1 diabetes (T1D). We hypothesized that CD4(+) T cell turnover would be greater in type 1 diabetes subjects compared to controls. In vitro studies of T cell function are unable to evaluate dynamic aspects of immune cell homoeostasis. Therefore, we used deuterium oxide ((2) H(2)O) to assess in vivo turnover of CD4(+) T cell subsets in T1D (n = 10) and control subjects (n = 10). Serial samples of naive, memory and regulatory (T(reg)) CD4(+) T cell subsets were collected and enrichment of deoxyribose was determined by gas chromatography-mass spectrometry (GC-MS). Quantification of T cell turnover was performed using mathematical models to estimate fractional enrichment (f, n = 20), turnover rate (k, n = 20), proliferation (p, n = 10) and disappearance (d*, n = 10). Although turnover of T(regs) was greater than memory and naive cells in both controls and T1D subjects, no differences were seen between T1D and controls in T(reg) or naive kinetics. However, turnover of CD4(+) memory T cells was faster in those with T1D compared to control subjects. Measurement and modelling of incorporated deuterium is useful for evaluating the in vivo kinetics of immune cells in T1D and could be incorporated into studies of the natural history of disease or clinical trials designed to alter the disease course. The enhanced CD4(+) memory T cell turnover in T1D may be important in understanding the pathophysiology and potential treatments of autoimmune diabetes.

Tumour necrosis factor-alpha induces cyclo-oxygenase-2 gene expression in first trimester trophoblasts: suppression by glucocorticoids and NSAIDs.

Tumour necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine which stimulates the synthesis and release of prostaglandins (PGs) in several in vitro and in vivo models of preterm labour. While TNF-alpha simulated PG production has been described in decidual, amnion and myometrial cells, to date no studies have focused on the role of TNF-alpha in the stimulation of arachidonic acid metabolism in placental trophoblast cells. Cyclo-oxygenase-2 (COX-2) is the rate-limiting enzyme in PG biosynthesis and is expressed de novo during cellular activation by cytokines. To test whether TNF-alpha alters expression of COX-2, trophoblasts from first trimester chorionic vili were cultured as a continuous cell line and treated with TNF-alpha alone or with TNF-alpha and dexamethasone (Dex). Total RNA and protein were extracted from the trophoblasts and subjected to Northern and immunoblot analysis, respectively. Northern blots were hybridized with a 32P-labelled probe encoding the COX-2 cDNA and immunoblots were incubated with anti-COX-2 antibodies. There was a time- and dose-dependent increase in COX-2 mRNA and protein expression in cells stimulated with TNF-alpha. The effect of TNF-alpha on COX-2 mRNA and protein expression was inhibited by dexamethasone (Dex). To examine the production of PGE2 and PGF(2 alpha), specific RIAs were performed on culture media from similarly stimulated cells. PG accumulation after TNF-alpha stimulation occurred in a time- and dose-dependent fashion with a similar inhibition of PG accumulation after Dex exposure. To be certain that TNF-alpha stimulated PGE2 production was, indeed, a result of COX-2 induction, RIAs were carried out with the COX-2-selective inhibitor NS-398. Cells stimulated with the NS-398 after TNF-alpha exposure demonstrated suppression of TNF-alpha-stimulated PGE2 formation. The results suggest that TNF-alpha elicits part of its pathophysiologic effects in preterm labour via alterations in COX-2 gene expression within the placental microenvironment.

Bottlenosed dolphin and human recognition of veridical and degraded video displays of an artificial gestural language.

2 bottlenosed dolphins proficient in interpreting gesture language signs viewed veridical and degraded gestures via TV without explicit training. In Exp. 1, dolphins immediately understood most gestures: Performance was high throughout degradations successively obscuring the head, torso, arms, and fingers, though deficits occurred for gestures degraded to a point-light display (PLD) of the signer's hands. In Exp. 2, humans of varying gestural fluency saw the PLD and veridical gestures from Exp. 1. Again, performance declined in the PLD condition. Though the dolphin recognized gestures as accurately as fluent humans, effects of the gesture's formational properties were not identical for humans and dolphin. Results suggest that the dolphin uses a network of semantic and gestural representations, that bottom-up processing predominates when the dolphin's short-term memory is taxed, and that recognition is affected by variables germane to grammatical category, short-term memory, and visual perception.

Autoimmune diseases in pregnancy. The obstetrician's view.

Pregnancy in the patient with an autoimmune disease is a high-risk situation often resulting in preterm delivery or pregnancy loss. Pregnancy loss can occur in any trimester. These patients require special maternal and fetal surveillance by the obstetrician. Patients with normal renal function and blood pressure are associated with the best outcome. Cooperation between the obstetrician, rheumatologist, and pediatrician usually result in a good outcome for both mother and infant.

Transvaginal cerclage under ultrasound guidance in cases of severe cervical hypoplasia.

Transabdominal cervical cerclage has been advocated for patients with cervical incompetence whose cervix is flush against the vaginal wall. Although several series of successful transabdominal cerclage have been reported, the morbidity of this technique precludes its routine use. We describe five pregnancies in four patients with extreme cervical hypoplasia who underwent successful prophylactic transvaginal cerclage placement at 12-13 weeks' gestation. All patients had a history of intrauterine diethylstilbestrol exposure, and three patients had also undergone cervical conization. In each case, using continuous transabdominal ultrasound guidance, the supravaginal cervix was dissected and two nonabsorbable sutures were placed through the cervix at right angles at the level of the anatomical internal os. There were no perioperative complications, and except for one patient who developed severe preeclampsia at 33 weeks, all patients delivered at term. We believe that the use of ultrasound in cases of severe cervical hypoplasia allows safe transvaginal cerclage placement, obviating the need for abdominal cerclage.

Prostaglandin E2 cervical ripening without subsequent induction of labor.

OBJECTIVE: To determine whether outpatient administration of intracervical prostaglandin (PG) E2 gel decreases the interval to delivery and duration of labor. METHODS: A randomized, double-blind, placebo-controlled trial compared the intracervical placement of 0.5 mg PGE2 gel with placebo in 61 pregnant women at 38 weeks' or greater gestation with Bishop scores less than 9. Transvaginal cervical length, fetal fibronectin, and Bishop score were assessed before gel placement. Subjects were then allowed to go into spontaneous labor unless an indication for induction developed. RESULTS: Thirty women were assigned to PGE2 and 31 to placebo. There were no significant demographic differences between the groups and there were no differences in cervical length, fetal fibronectin status, or Bishop scores. Fifteen women in the PGE2 group and five in the placebo group went into labor and delivered within the first 2 days after gel placement (P = .007). The median interval to delivery was significantly shorter in the PGE2 group, at 2.5 days, compared with placebo, at 7 days (P = .02). Nulliparas in the PGE2 group had a median interval to delivery of 2 days, compared with 7 days for nulliparas receiving placebo (P = .03). Active phases of labor were significantly shorter in the PGE2 group and for women with a negative fetal fibronectin test who received PGE2. CONCLUSION: Outpatient administration of intracervical PGE2 gel shortened intervals to delivery and shortened labor.

The seroprevalence of the rubeola antibody in a prenatal screening program.

OBJECTIVE: To evaluate the seroprevalence of the rubeola (measles) antibody in several obstetric populations. METHODS: In this cross-sectional study, women presenting for prenatal care underwent measurement of antibodies to the rubeola virus. The study population presented for care at either an urban medical center (group I) or a suburban medical center (group II). These groups were divided further into those receiving care in a resident-supervised clinic (A) and those in a private-practice setting (B). RESULTS: A total of 768 women were tested. Seventy-five (9.8%) women had rubeola antibody titers less than or equal to 0.13 and were classified as seronegative. The lowest percentage of seronegative women (3.2%) was found at the urban resident-supervised clinic site. The highest percentage of seronegative women (20.5%) was found in the suburban resident-supervised clinic site. Women classified as seronegative were younger, with a mean age of 25.0 years. No significant difference was observed based on gravidity, parity, or care received in an urban versus suburban private-practice setting. CONCLUSION: We suggest that an appreciable number of women presenting for prenatal care may lack antibodies to the rubeola virus. In the interest of personal and public health, populations believed to be at risk may benefit from ongoing surveillance of immune status and appropriate vaccination. Additional study is necessary to define best those groups that would benefit from surveillance and vaccination.

Pregnancy outcome of patients with uncorrected uterine anomalies managed in a high-risk obstetric setting.

During an 8-year period, we managed 42 women with 101 pregnancies with previously diagnosed but uncorrected uterine malformations referred to our institution for high-risk obstetric care. All patients were managed under the same standardized protocol requiring weekly visits and decreased physical activity. The population studied consisted of four groups of pregnancies with the following uterine anomalies: unicornuate (five), bicornuate (61), septate (25), and didelphys (ten). Sixty percent of the pregnancies in the unicornuate and didelphys group reached term, 39% in the bicornuate group, and 48% in the septate group. Preterm labor requiring tocolysis occurred in 21% of the pregnancies in the bicornuate group and 15% of the pregnancies in the septate group. Cerclage was placed in 5% of the pregnancies in the bicornuate group. Before our care, the fetal survival rate for pregnancies in the bicornuate and septate groups was 52 and 53%, respectively; with our management protocol, it was 58 and 65%, differences that were not statistically significant. Our experience suggests that high-risk obstetric intervention does not obviate the potential benefit of metroplasty, especially for patients with a bicornuate or septate uterus. We believe that traditional indications for metroplasty should continue to be used.

Perinatal outcome and long-term follow-up associated with modern management of diabetic nephropathy.

OBJECTIVE: To determine outcomes in pregnancies complicated by class F diabetes mellitus cared for at a single center, and to assess renal function in these women. METHODS: A retrospective review (1988-1994) of all pregnant women with class F diabetes was performed, as well as an evaluation of current renal function. RESULTS: Forty-six pregnancies in 45 women reached a mean (+/- standard deviation) gestational age of 35.8 +/- 2.3 weeks, with a mean birth weight of 2623 +/- 818 g. No deliveries occurred before 30 weeks and 39 (84%) were at least 34 weeks. Perinatal survival was 100%. Women with initial serum creatinine exceeding 1.5 mg/dL or more than 3 g/24 hours proteinuria had an increased risk of early delivery, lower birth weight, preeclampsia, and cesarean delivery. Twenty-four individuals (53%) developed preeclampsia and seven met criteria for severe preeclampsia. By the third trimester, 26 women(58%) had greater than a 1 g/24 hour increase in proteinuria and 16 (36%) demonstrated more than a 15% fall in creatinine clearance. Follow-up was obtained in 34 subjects with a mean duration of 2.8 years. Individuals with initial creatinine clearance greater than 90 mL/minute and less than 1 g of protein per 24 hours had less loss of renal function at follow-up, as measured by creatinine clearance. At follow-up, mean protein excretion had decreased 1.9 g/24 hours from third-trimester values, but eight women (24%) maintained protein excretion exceeding 3 g/24 hours. CONCLUSION: Modern management of class F patients can result in good perinatal outcomes. Renal function studies early in pregnancy can be used to define the risk of perinatal morbidity and long-term progression of renal disease.

The utility of the TDx test in the assessment of fetal lung maturity.

Accurate assessment of fetal lung maturity is essential in the management of high-risk obstetric patients. New rapid techniques have been developed to supplement time-consuming chromatographic methods. We compared one of these newer methods, the TDx-FLM, to the standard tests for fetal pulmonary maturity. There was an excellent correlation between the TDx and the lecithin-sphingomyelin ratio (r = 0.78). Although a TDx value of 70 or greater is considered mature, we found a value of 50 or greater predictive of fetal lung maturity in 100% of cases, and have chosen to redefine a mature value as 50 or greater in our institution. This value has greatly enhanced the clinical applicability of the test, allowing use of a large number of specimens from the previously poorly understood and often disregarded borderline category.

Interleukin-1 alpha, epidermal growth factor, and transforming growth factor-beta exhibit differential kinetics on endothelin-1 synthesis in amnion cells.

OBJECTIVE: To investigate the effects of three cytokines, interleukin-1 alpha (IL-1 alpha), epidermal growth factor (EGF), and transforming growth factor-beta (TGF-beta), on the regulation of endothelin-1 (ET-1) mRNA and protein production in human amnion cells. METHODS: Human amnion cells were harvested from uncomplicated pregnancies undergoing elective cesarean delivery at term and grown in primary monolayer culture. Cells were treated with IL-1 alpha, EGF, and TGF-beta for dose-response and time course experiments. Northern analysis was used to determine ET-1 mRNA expression, and enzyme-linked immunosorbent assay was used for ET-1 peptide determination. RESULTS: Interleukin-1 alpha, EGF, and TGF-beta induced the expression of ET-1 mRNA and protein in a dose- and time-dependent fashion. The kinetics of ET-1 mRNA production did not differ markedly with respect to the inducing cytokine, but the kinetics of ET-1 protein production was quite different. Interleukin-1 alpha and EGF stimulated a rapid increase in ET-1 that peaked by 24 hours, and the levels declined to just above the detection limit by 72 hours. In contrast, TGF-beta-stimulated cells showed modest ET-1 production at early times (4-24 hours) and then gradually increased and peaked at 72 hours. CONCLUSIONS: Cytokines modulate the expression of ET-1 mRNA and its cognate protein in human amnion cells. The differential kinetics of ET-1 peptide expression in amnion cells suggests that ET metabolism as well as synthesis contribute to the net expression of endothelin in amnion.

Do conversational hand gestures communicate?

In 5 experiments, male and female undergraduates viewed gestures and tried to select the words that originally accompanied them; read interpretations of gestures' meanings and tried to select the words that originally had accompanied them; tried to recognize gestures they previously had seen, presented either with or without the accompanying speech; and assigned gestures and the accompanying speech to semantic categories. On all 4 tasks, performance was better than chance but markedly inferior to performance when words were used as stimuli. Judgments of a gesture's semantic category were determined principally by the accompanying speech rather than gestural form. It is concluded that although gestures can convey some information, they are not richly informative, and the information they convey is largely redundant with speech.

Technique of varicose vein surgery.

A technique for varicose vein surgery is described which allows maximum removal of varicose veins and the trunks draining into them. Hemostasis by means of tantalum clips allows for distal ligation of branches beyond their bifurcations in sites of difficult access. This results in minimal blood loss and enables subdivision of collateral veins to prevent recurrence of varicosities.

Evolution of the in situ bypass.

The origins of the in situ vein bypass in Montreal, Canada and in London, England, are described. The subsequent evolution of the original techniques in Europe and the United States are followed. The condemnation of the procedure in the United States in 1969 is noted. The persistence of Cartier in Montreal and Hall in Norway and the revival of interest in the procedure by Leather and Karmody in Albany, New York, is recounted. The pathophysiologic basis for the complications of the method are analyzed and the measures by which they are currently remedied are shown. The method's present superiority is reported. The initial rejection and slow acceptance of this method is explained in terms of the special conditions attendant on its introduction and the attitudes of surgeons to new procedures.

Diagnosis and management of arterial mural thromboemboli.

If ischemic lesions or cerebral dysfunction appear without obvious cause, aneurysm, stenosing, or ulcerative plaques in proximal arteries are suspected. Diagnostic methods are outlined. Treatment by removal of the embolic source is preferred and exclusion of the lesion and bypass is reserved for inacessible lesions or poor operative risks.

A new button for retention suture fixation.

A button that may be snapped on and off the end of a retention suture has been described. It allows the tension on the suture to be adjusted easily, increases patient comfort, and avoids circumferential compression of the wound.