Nontraumatic Fat Embolism Found Following Maternal Death after Cesarean Delivery.

Introduction Fat embolism is a rare form of nonthrombotic embolization. Limited literature exists regarding the diagnosis of fat embolism during the perinatal period. We present the first case of maternal death that resulted from nontraumatic fat embolization following Cesarean delivery. Case Description A 29-year-old gravida 1 with a complex medical and surgical history underwent a primary Cesarean delivery at term. On postoperative day 2 the patient was found to be unresponsive. Despite resuscitative efforts, the patient succumbed. Autopsy findings were remarkable for diffuse pulmonary fat emboli. Furthermore, there was no histological evidence of either amniotic fluid embolism or thromboembolism. The primary cause of death was attributed to nontraumatic fat embolization. Discussion Multiple risk factors may have contributed to the development of nontraumatic fat embolization in our patient. Obstetricians should maintain a high level of suspicion for nontraumatic fat embolization in cases of maternal respiratory decompression and sudden maternal mortality.

Thoracic ganglioneuromas resulting in nonimmune hydrops fetalis.

Introduction Most often, ganglioneuromas affect older pediatric and adult patients. They are typically slow growing tumors that remain clinically silent until they become large enough to cause symptoms by compression of adjacent structures. Case We report a case of a 22-year-old Hispanic gravida 2 para 1 female patient who was found to have massive hydrops fetalis at 20 completed gestational weeks. Fetal echocardiography revealed a narrowed distal ductal arch and proximal descending aorta. Cesarean delivery was undertaken at 29 completed gestational weeks for refractory labor and nonreassuring fetal status. The neonate expired at 47 minutes of life despite aggressive resuscitation. At autopsy, multiple thoracic masses were found adjacent to a compressed proximal descending aorta. Histological and immunohistochemical analysis confirmed the diagnosis of a ganglioneuroma, a rare type of neural crest tumor. Discussion A variety of intrathoracic masses have previously been reported to cause hydrops fetalis including teratomas, fibrosarcomas, and lymphangiomas. To our knowledge, this case is the first description of hydrops fetalis caused by ganglioneuromas. We propose that multiple thoracic ganglioneuromas led to biventricular distal outflow tract obstruction and hydrops fetalis.

Uterine artery Doppler in first-trimester pregnancy screening.

Uterine artery Doppler velocimetry has revolutionized the investigation of the developing placental vasculature. Abnormal placental vascular development is the basis of common obstetric disorders such as preeclampsia and intrauterine growth restriction. Uterine artery Doppler velocimetry by itself or in combination with other biochemical markers seems to be an effective first-trimester screening tool for preeclampsia and in particular early-onset preeclampsia. The diagnostic accuracy although statistically significant, is not as high for the prediction of intrauterine growth restriction unrelated to preeclampsia. In the future, first-trimester prophylaxis using antiplatelet agents in Doppler identified high-risk groups could suppress the development of these disorders.

Complete trisomy 21 vs translocation Down syndrome: a comparison of modes of ascertainment.

OBJECTIVE: To compare the indications for invasive prenatal testing resulting in the detection of translocation Down syndrome and complete trisomy 21. STUDY DESIGN: This case control study was based on a large amniocentesis and chorionic villi samples database (n = 534,795). All specimens with translocation Down syndrome (n = 203) comprised the translocation group and were compared with a maternal age-matched group (4 to 1, n = 812) in which complete trisomy 21 was detected. Women with a normal karyotype were randomly selected (n = 812) and served as controls. Indications for invasive testing were compared among the 3 paired groups using χ(2) analysis. RESULTS: There were no differences in the incidence of abnormal first- and second-trimester screening tests between the translocation Down syndrome and the complete trisomy 21 groups. History of prior aneuploidy was significantly more frequent in the translocation Down syndrome group, as compared with either complete trisomy 21 fetuses or normal controls. CONCLUSION: Fetuses with translocation Down syndrome present with the same screening abnormalities as fetuses with complete trisomy 21.

Amniotic fluid sTREM-1 in normal pregnancy, spontaneous parturition at term and preterm, and intra-amniotic infection/inflammation.

OBJECTIVE: Intra-amniotic infection/inflammation (IAI) is one of the most important mechanisms of disease in preterm birth. Triggering receptor expressed on myeloid cells (TREM)- 1 is a transmembrane glycoprotein expressed by neutrophils, macrophages and mature monocytes. TREM-1 is upregulated in biological fluids and tissues infected by Gram (+) and Gram (-) bacteria and fungi, amplifies the production of pro-inflammatory cytokines and chemokines, and its soluble form (sTREM-1) is released in the presence of infection. The aim of this study was to determine the effect of gestational age, parturition (term and preterm) and IAI in the amniotic fluid (AF) concentrations of sTREM-1. STUDY DESIGN: This cross-sectional study included 434 patients in the following groups: (1) mid-trimester of pregnancy (14-18 weeks, n = 38); (2) normal pregnant women at term with (n = 39) and without (n = 39) labor; (3) patients with spontaneous preterm labor (PTL) and intact membranes classified into: (a) PTL who delivered at term (n = 99); (b) PTL who delivered preterm (<37 weeks gestation) without IAI (n = 80); and (c) PTL with IAI (n = 59); and (4) women with preterm prelabor rupture of membranes (PROM) with (n = 40) and without (n = 40) IAI. The AF concentration of sTREM-1 was determined by enzyme-linked immunoassay. Non-parametric statistics were used for analyses. RESULTS: (1) sTREM-1 was detected in all the AF samples; (2) the median AF sTREM-1 concentration at term was higher than in the mid-trimester (4277.6 pg/ml vs. 1140.4 pg/ml; p < 0.001); (3) among patients with PTL, the median AF sTREM-1 concentration was higher in patients with IAI than in those without IAI (6154.4 pg/ml vs. 3282.8 pg/ml; p < 0.001) and those with PTL who delivered at term (6154.4 pg/ml vs. 2794 pg/ml; p < 0.001); (4) patients with preterm PROM with IAI had a higher median AF sTREM-1 concentration than those without IAI (7893.1 pg/ml vs. 3386.6 pg/ml; p < 0.001); (5) no differences were observed in the median AF sTREM-1 concentration between patients with spontaneous labor at term and those at term not in labor (4712.4 pg/ml vs. 4277.6 pg/ml; respectively p = 0.4); and 6) an AF sTREM-1 concentration >or=6416 pg/ml (derived from a ROC curve) had a sensitivity of 72% and a specificity of 89% for the diagnosis of intra-amniotic infection. CONCLUSIONS: sTREM-1 is a physiologic constituent of the AF, and its concentration: (1) is significantly elevated in the presence of IAI; (2) increases with advancing gestation; and (3) does not change in the presence of spontaneous labor at term. We propose that sTREM-1 play a role in the innate immune response against intra-amniotic infection.

Amniotic fluid soluble human leukocyte antigen-G in term and preterm parturition, and intra-amniotic infection/inflammation.

OBJECTIVE: Circulating soluble human leukocyte antigen-G (sHLA-G) has been associated with pregnancy complications, and determination of sHLA-G concentrations in amniotic fluid (AF) has been reported in normal pregnancies. Our aim was to determine if the AF concentrations of sHLA-G change with advancing gestation, spontaneous labor at term, and in patients with spontaneous preterm labor (PTL) with intact membranes, as well as in those with preterm prelabor rupture of membranes (PROM), in the presence or absence of intra-amniotic infection/inflammation (IAI). STUDY DESIGN: This cross-sectional study included the following groups: (1) mid-trimester (n = 55); (2) normal pregnancy at term with (n = 50) and without (n = 50) labor; (3) spontaneous PTL with intact membranes divided into: (a) PTL who delivered at term (n = 153); (b) PTL who delivered preterm without IAI (n = 108); and (c) PTL with IAI (n = 84); and (4) preterm PROM with (n = 46) and without (n = 44) IAI. sHLA-G concentrations were determined by ELISA. Non-parametric statistics were used for analysis. RESULTS: (1) Among patients with PTL, the median AF sHLA-G concentration was higher in patients with IAI than in those without IAI or women that delivered at term (p < 0.001 for both comparisons); (2) Similarly, patients with preterm PROM and IAI had higher median AF sHLA-G concentrations than those without IAI (p = 0.004); (3) Among patients with PTL and delivery, those with histologic chorioamnionitis and/or funisitis had a higher median AF sHLA-G concentration than those without histologic inflammation (p < 0.001); and (4) The median AF sHLA-G concentration did not change with advancing gestational age. CONCLUSIONS: AF sHLA-G concentrations are elevated in preterm parturition associated to IAI as well as in histologic chorioamnionitis. We propose that sHLA-G may participate in the regulation of the host immune response against intra-amniotic infection.

Preterm labor biomarker discovery in serum using 3 proteomic profiling methodologies.

OBJECTIVE: The aim of this study was to identify changes in protein expression in normal pregnancy compared with preterm labor by using 3 proteomic methods. STUDY DESIGN: Serum was collected from 25 nonpregnant (n = 5) and pregnant women at 24-40 weeks' gestation (n = 20) who had preterm labor resulting in preterm delivery (n = 5), preterm labor with term delivery (n = 5), term labor resulting in delivery (n = 5), or at term with contractions (n = 5). Undepleted serum was used for surface-enhanced laser desorption ionization and immune-depleted serum for matrix-assisted laser desorption ionization and 2-dimensional electrophoresis. RESULTS: Surface-enhanced laser desorption ionization identified significantly different peaks between preterm labor resulting in preterm delivery vs term labor resulting in delivery and preterm labor resulting in preterm delivery vs preterm labor with term delivery using 4 surfaces. In preterm labor resulting in preterm delivery vs preterm labor with term delivery, a peak of 7783.2 m/z was significantly up-regulated and at 3164 m/z down-regulated on 3 surfaces. By using 2-dimensional electrophoresis, protein 5364 was significantly different between preterm labor resulting in preterm delivery and term labor resulting in delivery. In preterm labor resulting in preterm delivery, 6 proteins showed decreasing trend and 1 showed increasing trend vs preterm labor with term delivery. Matrix-assisted laser desorption ionization showed a striking difference at 55,000 m/z between preterm labor resulting in preterm delivery and term labor resulting in delivery. CONCLUSION: Surface-enhanced laser desorption ionization identified 2 proteins fulfilling the criteria of putative biomarkers. Biomarker identification may aid in identifying women with preterm labor who will deliver preterm.

Dysregulation of maternal serum adiponectin in preterm labor.

OBJECTIVE: Intra-amniotic and systemic infection/inflammation have been causally linked to preterm parturition and fetal injury. An emerging theme is that adipose tissue can orchestrate a metabolic response to insults, but also an inflammatory response via the production of adipocytokines, and that these two phenomenons are interrelated. Adiponectin, an insulin-sensitising, anti-inflammatory adipocytokine, circulates in multimeric complexes including low-molecular weight (LMW) trimers, medium-molecular weight (MMW) hexamers and high-molecular weight (HMW) isoforms. Each of these complexes can exert differential biological effects. The aim of this study was to determine whether spontaneous preterm labor (PTL) with intact membranes and intra-amniotic infection/inflammation (IAI) is associated with changes in maternal serum circulating adiponectin multimers. STUDY DESIGN: This cross-sectional study included patients in the following groups: (1) normal pregnant women (n=158); (2) patients with an episode of preterm labor and intact membranes without IAI who delivered at term (n=41); (3) preterm labor without IAI who delivered preterm (n=27); and (4) preterm labor with IAI who delivered preterm (n=36). Serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. Non-parametric statistics were used for analyses. RESULTS: (1) Preterm labor leading to preterm delivery or an episode of preterm labor that does not lead to preterm delivery was associated with a lower median maternal serum concentration of total and HMW adiponectin, a lower median HMW/total adiponectin ratio and a higher median LMW/total adiponectin ratio than normal pregnancy; (2) among patients with preterm labor, those with IAI had the lowest median concentration of total and HMW adiponectin, as well as the lowest median HMW/total adiponectin ratio; (3) the changes in maternal adiponectin and adiponectin multimers remained significant after adjusting for confounding factors such as maternal age, BMI, gestational age at sampling and parity. CONCLUSION: (1) Preterm labor is characterised by a change in the profile of adiponectin multimers concentrations and their relative isoforms. These changes were observed in patients with an episode of preterm labor not leading to preterm delivery, in patients with intra-amniotic inflammation, or in those without evidence of intra-amniotic inflammation. (2) The changes in adiponectin multimer concentrations reported in preterm labor are different from those previously reported in spontaneous labor at term, suggesting that there is a fundamental difference between preterm labor and labor at term. (3) The findings reported herein provide the first evidence for the participation of adiponectin multimer in preterm parturition. We propose that adiponectins and adipokines in general provide a mechanism to organise the metabolic demands generated by the process of preterm parturition regardless of the nature of the insult (intra-amniotic inflammation or not).

Maternal serum adiponectin multimers in preeclampsia.

OBJECTIVE: Obesity, insulin resistance, and dyslipidemia are associated with preeclampsia. Recently, "adipose tissue failure", characterized by dysregulation of adipokine production, has been implicated in the pathophysiology of these metabolic complications. Adiponectin, an insulin-sensitizing, anti-atherogenic, anti-inflammatory and angiogenic adipokine, circulates in oligomeric complexes including: low-molecular-weight (LMW) trimers, medium-molecular-weight (MMW) hexamers and high-molecular-weight (HMW) isoforms. These multimers exert differential biological effects, and HMW to total adiponectin ratio (S(A)) has been reported to be a specific marker of adiponectin activity. The aim of this study was to determine whether preeclampsia is associated with changes in circulating adiponectin multimers. STUDY DESIGN: This cross-sectional study included women with: 1) normal pregnancy (n=225); and 2) patients with mild preeclampsia (n=111). The study population was further stratified by first trimester BMI (normal weight <25 kg/m(2) vs. overweight/obese >or=25 kg/m(2)). Serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. Non-parametric statistics were used for analysis. RESULTS: 1) The median maternal HMW and LMW adiponectin concentrations were lower in patients with preeclampsia than in those with normal pregnancies (P<0.001 and P=0.01, respectively); 2) patients with preeclampsia had a lower HMW/total adiponectin ratio (P<0.001) and higher MMW/total adiponectin and LMW/total adiponectin ratios than those with a normal pregnancy (P<0.001 and P=0.009, respectively); 3) the presence of preeclampsia was independently associated with lower maternal serum HMW adiponectin concentrations (P=0.001) and with a low HMW/total adiponectin ratio (P<0.001) after correction for maternal age, maternal BMI, the difference in BMI between the third and the first trimester, and gestational age at sampling; and 4) overweight/obese pregnant women had a lower median total and HMW adiponectin concentration than normal weight pregnant women among women with normal pregnancies, but not among those with preeclampsia. CONCLUSION: 1) Preeclampsia is associated with a lower median concentration of the HMW adiponectin isoform, the most active form of this adipokine, and a low HMW/total adiponectin ratio, a specific marker of adiponectin biologic activity; 2) in contrast to normal pregnancy, preeclampsia is not associated with decreased circulating adiponectin multimers in overweight/obese individuals suggesting altered regulation of this adipokine in preeclampsia; 3) collectively, these findings suggest that preeclampsia is characterized by alterations in adiponectin multimers and their relative distribution implying a role for adiponectin multimers in the mechanism of disease in preeclampsia.

Case series of rosiglitazone used during the first trimester of pregnancy.

Prior to 2007, use of the insulin sensitizer metformin was widely advocated in patients with polycystic ovarian syndrome (PCOS) both to promote ovulation and decrease the incidence of PCOS-associated obstetrical complications. However, the gastrointestinal disturbances associated with metformin led many to discontinue its use. Rosiglitazone is an insulin sensitizer that, because of minimal associated gastrointestinal disturbance, was used as an alternative to metformin in PCOS patients. From 2003 to 2005, 8 women with PCOS unable to tolerate metformin used rosiglitazone for ovulation induction and during their first 12 weeks of gestation. All delivered healthy babies at term, without obstetric complications or congenital anomalies. However, given recent evidence that disputes the reproductive benefits of insulin sensitization for PCOS and that raises safety concerns of rosiglitazone, we are no longer using it for PCOS treatment.

Postpartum headache: is your work-up complete?

OBJECTIVE: Headache is a common finding in the postpartum period, and there are limited data describing the cause and treatment of women with postpartum headache. Our objective was to describe our experience with women who were hospitalized for postpartum headache and to develop a management algorithm for these women. STUDY DESIGN: Data for 95 women with headache >24 hours after delivery from 2000-2005 were reviewed retrospectively. Maternal assessment included an evaluation for benign and serious causes of headache that included preeclampsia, dural puncture, and neurologic lesions. Neurologic imaging were performed on the basis of initial neurologic findings and clinical course. Outcomes that were studied included cause, a need for cerebral imaging, neurologic findings, maternal complications, and long-term follow-up evaluations. RESULTS: The mean onset of headache was 3.4 days (range, 2-32 days) after delivery. Tension-type/migraine headache was the most common cause (47%). Preeclampsia/eclampsia and spinal headache comprised 24% and 16% of cases, respectively. Anesthesia evaluation was required in 15 patients because of suspected spinal headache; blood patch was required in 12 of these patients. Cerebral imaging was performed in 22 patients because of focal neurologic deficits and/or failure to respond to initial therapy; 15 of these women (68%) had abnormal findings. Ten patients had serious cerebral pathologic findings, such as hemorrhage, thrombosis, or vasculopathy. There were no deaths; 2 women had minor residual neurologic damage on follow-up evaluation. CONCLUSION: The evaluation of persistent headaches that develop >24 hours after delivery must be performed in a stepwise fashion and requires a multidisciplinary approach. Preeclampsia should be considered initially in women with hypertension and proteinuria. Normotensive women should be evaluated initially for tension-type/migraine headache or spinal headache. Patients with headache that is refractory to usual therapy and patients with neurologic deficit require cerebral imaging to detect the presence of life-threatening causes.