Joel Baron

Lower circulation levels and activity of α-1 Antitrypsin in pregnant women with severe preeclampsia

Objective: α-1 antitrypsin (AAT) is an anti-protease, anti-inflammatory and tissue-protective molecule. Normal circulating levels are <3.5 mg/dl and rise during pregnancy. Although AAT deficiency is associated with several pregnancy and placental disorders, little is known regarding AAT levels and preeclampsia. Since unopposed inflammation might contribute to preeclampsia, we studied whether preeclampsia is associated with lower than normal levels and activity of AAT. Methods: In a prospective case-control study, we compared maternal serum AAT activity and levels between patients with severe preeclampsia (n = 23) and without preeclampsia (n = 18). Results: AAT levels were 1.91 ± 0.08-fold lower in the preeclampsia group compared to healthy group (3.854 ± 0.26 vs. 7.397 ± 0.34 mg/ml; p < 0.001), and correlated with protease inhibitory capacity (46.56 ± 2.08% vs. 67.08 ± 1.74%; p < 0.001). Conclusions: Our findings show association between lower AAT levels and severe preeclampsia during pregnancy. Further studies are required to identify the mechanism behind the association, and the possibility of safe AAT augmentation for individuals with insufficient circulating AAT.

The consequences of previous uterine scar dehiscence and cesarean delivery on subsequent births

To determine whether women with a previous uterine scar dehiscence are at increased risk of adverse perinatal outcomes in the following delivery.

Low levels of circulating alpha-1 antitrypsin are associated with spontaneous abortions

Abstract Objective: Alpha-1 antitrypsin (AAT), a circulating anti-inflammatory molecule, rises four- to sixfold during acute phase responses and during pregnancy. AAT deficiency is linked with various pregnancy complications. The aim of this study is to determine plasma concentrations and activity of AAT and serum cytokine levels in blood samples from women undergoing spontaneous abortions as compared with elective abortions. Methods: A prospective case–control study consisted of patients with sporadic abortions (n = 15), recurrent spontaneous abortions (n = 14) and healthy pregnancies going through elective terminations (n = 11). Circulating AAT and cytokine levels were determined before dilatation and curettage. Results: AAT levels were lower in both recurrent and sporadic spontaneous abortion groups compared with healthy pregnancies (1.421 ± 0.08, 1.569 ± 0.14 and 3.224 ± 0.45 mg/ml, respectively, p < 0.001). Reduced AAT levels correlated with elevated proinflammatory cytokines. Conclusions: AAT levels in patients with either sporadic or recurrent spontaneous abortions were lower than normal pregnancies, and were associated with an inflammatory profile. Future studies should examine larger cohort groups, effects of earlier time-points and the influence of antithrombotic therapy in such patients who are diagnosed with relatively low levels of circulating AAT, in an effort to improve pregnancy outcomes.

Umbilical artery blood flows among pregnancies with single umbilical artery: a prospective case-control study

Abstract Objectives: To evaluate peak systolic velocity (PSV) in the umbilical artery (UA) among patients with single umbilical artery (SUA) as compared with patients with three vessel cords. Methods: A prospective case-control study was performed. UA blood flow velocimetry was obtained from fetuses with SUA and from a control group with three vessel cord. PSV and pulsatility index (PI) were measured. Patients’ characteristics were compared for statistical differences and a linear regression model was constructed for the different groups. Results: UA Doppler velocimetry measurements were obtained from 29 patients with SUA and from 29 controls matched for gestational age. The differences between UA PI with and without SUA were significant (F = 3.471; p = 0.0379) showing a lower PI in the SUA group. However, no significant statistical difference was found in PSV between these two groups (F = 0.149; p = 0.86). Conclusions: While the impedance in the UA of patients with a SUA was lower compared with patients with a normal umbilical cord, the PSV did not differ.

Postpartum uterine artery Doppler velocimetry among patients following a delivery complicated with preeclampsia

Objective: To evaluate postpartum uterine artery (UtA) velocimetry in patients following severe preeclampsia (PET) as compared with normotensive controls. Study Design: Postpartum UtA velocimetry was obtained prospectively during the early postpartum period. The right and left UtA pulsatility index (PI) was measured and the presence of an early diastolic notch was noted. For categorical variables, the χ2 test or Fisher exact was used as appropriate and for continuous variables the t-test was used. The p value <0.05 was considered statistically significant. Results: Thirty-one patients following severe PET and 52 normotensive controls were included in the study. Following severe PET, higher rates of intrauterine growth restriction, cesarean delivery, preterm delivery and accordingly lower neonatal birth weight were noted. Postpartum UtA velocimetry measurements were performed on average 51.2 h after delivery (range 8–169). Right and left UtA PI was comparable between patients following severe PET and controls. The presence of unilateral and bilateral early diastolic notches were significantly higher in patients following severe PET. Conclusions: The pathophysiology of uterine involution and the physiologic return of the uterine arteries to the non-pregnant state may be different following severe PET.

α1-Antitrypsin insufficiency is a possible contributor to preterm premature rupture of membranes

Objective: α1-Antitrypsin (AAT) is protective of tissue damage induced by enzymes of inflammatory cell source. Inflammatory cells are involved in preterm labor, preterm premature rupture of membrane (PPROM) and term premature rupture of membrane (PROM). The purpose of this research was to examine whether plasma concentration and activity of AAT differ between these manifestations. Methods: In a prospective case control study, blood samples were assayed for AAT concentration and activity in 71 individuals. AAT concentration and activity were measured by standard methods. Results: No significant differences were found between AAT levels (p = 0.497) and activity (p = 0.879) in preterm and term labor. AAT levels and activity in PPROM and PROM were not significantly different as well (p = 0.748 and p = 0.880, respectively). While 69 out of 71 patients displayed normal circulating levels of AAT, 2 PPROM patients out of 15 had abnormally low, previously undiagnosed,AAT concentrations, and had subsequently developed complications that were absent in the other groups. Conclusions: No statistically significant differences were demonstrated in the levels of AAT between patients with preterm and term labor, nor between preterm and term PROM. Yet, unexpectedly, patients that had marked AAT deficiency belonged exclusively to the PPROM group.

Ultrasonographic approach to diagnosis of fetal inflammatory response syndrome: a tool for at-risk fetuses?

Preterm parturition is a syndrome that may result from many underlying mechanisms. Infection and inflammation are the prominent ones. Intrauterine infection and inflammation have an effect akin to sepsis, and that is similar to systemic inflammatory response in adults. Indeed, there is evidence to support the association of a fetal inflammatory response syndrome (FIRS) to systemic infection and inflammation. The utilization of invasive procedures for the prenatal diagnosis of FIRS is associated with a risk for complications resulting from the invasive method. The progress in the imaging quality of obstetrical ultrasound and the development of novel methods for functional anatomical assessment of the fetal organs may help to identify, noninvasively, fetuses at risk for FIRS in patients presenting with preterm labor. We review the studies describing advanced sonographic modalities and the imaging findings in the heart, thymus, kidney, adrenal glands, and spleen of these fetuses.

Diminished activity of circulating α1-antitrypsin is associated with pre-gestational isolated obesity.

Abstract Objective: To examine possible correlation between α1-antitrypsin (AAT) levels and activity in patients with and without obesity, after excluding complications such as gestational diabetes mellitus (GDM), during pregnancy. Study design: A prospective case–control study was conducted. AAT levels were determined by standard human AAT ELISA according to the manufacturers instructions. Elastase inhibition was determined by kinetic assay according to manufacturer recommendations. Assays were performed in duplicates and repeated twice for each sample in separate sessions. Patients with diabetes mellitus were excluded from the study. The Mann–Whitney U-test was performed in order to determine statistical differences between the groups, and AAT concentration and activity. Results: During the study period, 43 patients were recruited: 21 with isolated obesity and 22 non-obese parturients (control group). According to ELISA, AAT concentrations were mildly lower in obese women compared with non-obese women (8.31 ± 0.28 mg/ml versus 9.5 ± 0.37 mg/ml, p = 0.0155). However, the elastase inhibitory capacity was markedly lower in obese versus non-obese parturients (mean 27.33 ± 2.08 % versus 43.73 ± 3.1%, p < 0.001). Conclusions: Isolated obesity in pregnancy is associated with lower activity of AAT. These findings correlate with the reduced concentration and activity of AAT found in patients with GDM. Accordingly, it might suggest an inflammatory axis shared by obesity and the development of insulin resistance.

Sonographic large fetal head circumference and risk of cesarean delivery

BACKGROUND: Persistently high rates of cesarean deliveries are cause for concern for physicians, patients, and health systems. Prelabor assessment might be refined by identifying factors that help predict an individual patients risk of cesarean delivery. Such factors may contribute to patient safety and satisfaction as well as health system planning and resource allocation. In an earlier study, neonatal head circumference was shown to be more strongly associated with delivery mode and other outcome measures than neonatal birthweight. OBJECTIVE: In the present study we aimed to evaluate the association of sonographically measured fetal head circumference measured within 1 week of delivery with delivery mode. STUDY DESIGN: This was a multicenter electronic medical record‐based study of birth outcomes of primiparous women with term (37‐42 weeks) singleton fetuses presenting for ultrasound with fetal biometry within 1 week of delivery. Fetal head circumference and estimated fetal weight were correlated with maternal background, obstetric, and neonatal outcome parameters. Elective cesarean deliveries were excluded. Multinomial regression analysis provided adjusted odds ratios for instrumental delivery and unplanned cesarean delivery when the fetal head circumference was ≥35 cm or estimated fetal weight ≥3900 g, while controlling for possible confounders. RESULTS: In all, 11,500 cases were collected; 906 elective cesarean deliveries were excluded. A fetal head circumference ≥35 cm increased the risk for unplanned cesarean delivery: 174 fetuses with fetal head circumference ≥35 cm (32%) were delivered by cesarean, vs 1712 (17%) when fetal head circumference <35 cm (odds ratio, 2.49; 95% confidence interval, 2.04–3.03). A fetal head circumference ≥35 cm increased the risk of instrumental delivery (odds ratio, 1.48; 95% confidence interval, 1.16–1.88), while estimated fetal weight ≥3900 g tended to reduce it (nonsignificant). Multinomial regression analysis showed that fetal head circumference ≥35 cm increased the risk of unplanned cesarean delivery by an adjusted odds ratio of 1.75 (95% confidence interval, 1.4–2.18) controlling for gestational age, fetal gender, and epidural anesthesia. The rate of prolonged second stage of labor was significantly increased when either the fetal head circumference was ≥35 cm or the estimated fetal weight ≥3900 g, from 22.7% in the total cohort to 31.0%. A fetal head circumference ≥35 cm was associated with a higher rate of 5‐minute Apgar score ≤7: 9 (1.7%) vs 63 (0.6%) of infants with fetal head circumference <35 cm (P = .01). The rate among fetuses with an estimated fetal weight ≥3900 g was not significantly increased. The rate of admission to the neonatal intensive care unit did not differ among the groups. CONCLUSION: Sonographic fetal head circumference ≥35 cm, measured within 1 week of delivery, is an independent risk factor for unplanned cesarean delivery but not instrumental delivery. Both fetal head circumference ≥35 cm and estimated fetal weight ≥3900 g significantly increased the risk of a prolonged second stage of labor. Fetal head circumference measurement in the last days before delivery may be an important adjunct to estimated fetal weight in labor management.

OC13.02: Fetal head circumference to predict delivery mode: a pilot study

Objectives: Fetal macrosomia is a perennial obstetric management problem. Macrosomia assessment is based mostly on clinically or sonographically EFW. We explored the impact of head circumference (HC) on obstetric outcomes including delivery mode and maternal and neonatal complications, as compared to birth weight, in order to improve the management of ‘‘big babies.’’ Methods: In several parallel cohort studies based on over 120,000 term singleton deliveries we analysed the association of HC with unplanned Caesarean delivery [UCD] and vacuum extraction (VE), failed vacuum, prolonged second stage of labour (PSSL), persistent occiput posterior (OP) position at delivery, levator ani avulsion, and neonatal outcomes including Apgar<7, umbilical artery pH≤7.1, and NICU admission. Results: When HC≥95th centile, the risks of PSSL, UCD, VE, failed vacuum, and neonatal complications, are significantly increased. Risk of levator ani avulsion is increased when HC≥90th centile. Results (OR and 95% CI) as compared with high birthweight are summarised in table 1. Conclusions: In several studies we have observed that large HC (≥90th or 95th centile) impacts on length of second stage, delivery mode, maternal pelvic floor trauma, and neonatal complications. OP position at delivery intensifies the effect of large HC. We propose that prelabour counselling and obstetric management take into account head circumference, along with other fetal and maternal parameters.