Hassan Harirah

Amniotic fluid matrix metalloproteinase-9 and interleukin-6 in predicting intra-amniotic infection

OBJECTIVE To assess the potential role of amniotic fluid (AF) matrix metalloproteinase‐9 and interleukin‐6 in predicting intra‐amniotic infection. METHODS Eighty‐four women with singleton gestations with preterm contraction, preterm labor, preterm premature rupture of membranes, or clinical suspicion of intra‐amniotic infection were studied. Amniotic fluid was obtained by transabdominal amniocentesis before starting any treatment. Intra‐amniotic infection was defined as the presence of a positive AF culture. Amniotic fluid glucose concentration, leukocytes, matrix metalloproteinase‐9, and interleukin‐6 were determined. RESULTS Amniotic fluid matrix metalloproteinase‐9 and interleukin‐6 levels were significantly higher in women with intra‐amniotic infection than in those without. With intra‐amniotic infection, levels of matrix metalloproteinase‐9 significantly correlated with interleukin‐6 (r = 0.813, P < .001). Each of matrix metalloproteinase‐9 and interleukin‐6 significantly correlated with AF leukocytes and inversely correlated with AF glucose. Using AF cutoff levels of 13.6 ng/mL for matrix metalloproteinase‐9 and 11.4 ng/mL for interleukin‐6, the sensitivity, specificity, and positive and negative predictive values for diagnosing intra‐amniotic infection were 77% versus 73%, 100% versus 79%, 100% versus 61%, and 90% versus 86%, respectively. Combining AF matrix metalloproteinase‐9 with interleukin‐6 slightly improved the sensitivity and the negative predictive values in diagnosing intra‐amniotic infection. CONCLUSIONS Amniotic fluid matrix metalloproteinase‐9 and interleukin‐6 are significantly elevated in women with intra‐amniotic infection. Amniotic fluid matrix metallo‐proteinase‐9 is an accurate biochemical marker in predicting intra‐amniotic infection with better sensitivity, specificity, and positive and negative predictive values than interleukin‐6.

Serum soluble Fas levels in preeclampsia

Objective To determine if serum soluble Fas levels are altered in women with preeclampsia. Methods Thirty-four pregnant women with preeclampsia and 34 normotensive pregnant women were studied. Subjects were matched as much as possible for demographics. Preeclampsia was defined as proteinuric hypertension. Serum soluble Fas levels were measured by enzyme-linked immunoassay. Two-tailed Student t test, χ2 test, Pearson correlation coefficients, and analysis of variance with post hoc test were used for statistical analyses. Results Mean serum soluble Fas levels were significantly higher in preeclamptic than normotensive women (10.59 ± 0.68 U/mL versus 5.65 ± 0.35 U/mL, P < .001). Conclusion Elevated serum soluble Fas is associated with preeclampsia. Such elevation might indicate protection of maternal T-lymphocyte apoptosis and consequently lead to the maternal immune intolerance noted in preeclampsia.

Prenatal Diagnosis of a Fetus with Unbalanced Translocation (4;13)(p16;q32) with Overlapping Features of Patau and Wolf-Hirschhorn Syndromes

Wolf-Hirschhorn syndrome (WHS) and Patau syndrome are two of the most severe conditions resulting from chromosome abnormalities. WHS is caused by a deletion of 4p16, while Patau syndrome is caused by trisomy for some or all regions of chromosome 13. Though the etiologies of these syndromes differ, they share several features including pre- and postnatal growth retardation, microcephaly, cleft lip and palate, and cardiac anomalies. We present here a female fetus with deletion of 4p16 → pter and duplication of 13q32 → qter due to unbalanced segregation of t(4;13)(p16;q32) in the father. She displayed overlapping features of both of these syndromes on ultrasound. To the best of our knowledge, this is the first report of a fetus with both partial trisomy 13 and deletion of 4p16, the critical region for WHS.

Effect of Gestational Age and Position on Peak Expiratory Flow Rate: A Longitudinal Study

OBJECTIVE: We sought to study the effects of gestational age and maternal position on peak expiratory flow rates. METHODS: Peak expiratory flow rates were measured in the standing, sitting, and supine positions in 38 healthy pregnant women at 4-week intervals starting at less than 10 weeks until delivery and again at 6 weeks postpartum. The highest reading of 3 consecutive peak expiratory flow rate measurements for each encounter and position was used in the analysis. Repeated measures analysis of covariance was performed with subjects, gestational age, position, and gestational age times position as the model effects. Least squares mean peak expiratory flow rates were compared among positions at different gestation ages using Bonferroni-adjusted least significant difference t tests. RESULTS: Peak expiratory flow rate declined significantly throughout gestation in all positions (P < .001) with mean rate of decline of 0.65 L/min per week). The slopes of linear trends were not statistically different between positions (P = .222). However, the rate of decline for the supine position was higher than for standing and sitting positions (0.86 compared with 0.46 and 0.57 L/min per week), respectively. On average, the postpartum peak expiratory flow rate returned to 71.9% of its measurement in early gestation. Nomograms depicting mean and the 5th and 95th percentiles of peak expiratory flow rates were constructed for each position. CONCLUSION: Peak expiratory flow rate measurements are affected by maternal position and advancing gestational age, especially in the supine position. Adjustment of patients flow rate in relation to gestational age and maternal position is recommended, especially in pregnant women with asthma. LEVEL OF EVIDENCE: III

Elevated expression of catechol-O-methyltransferase is associated with labor and increased prostaglandin E2 production by human fetal membranes

OBJECTIVE The purpose of this study was to evaluate the expression and function of catechol-O-methyltransferase in human fetal membranes at term. STUDY DESIGN Fetal membranes obtained from women between 38-42 weeks of gestation, after (1) vaginal delivery with spontaneous labor and (2) prelabor elective cesarean section (no labor), were assayed for catechol-O-methyltransferase expression using quantitative real-time polymerase chain reaction analysis, immunohistochemistry, and Western blot analysis. Prostaglandin E(2) secretion from amnion and choriodecidua explants treated with or without catechol-O-methyltransferase inhibitor was assayed by enzyme-linked immunosorbent analysis. RESULTS Amnion layer of fetal membranes from laboring women expressed significantly higher levels of catechol-O-methyltransferase, compared with those from women with no labor. Catechol-O-methyltransferase was higher in the amnion layer than in choriodecidua. Selective catechol-O-methyltransferase inhibition significantly decreased prostaglandin E(2) production from fetal membranes. CONCLUSION Labor increases catechol-O-methyltransferase expression in the amnion of human fetal membranes. Selective catechol-O-methyltransferase inhibition decreased prostaglandin E(2) secretion in fetal explant cultures, suggesting a role for catechol-O-methyltransferase in human labor and delivery.

Treatment with an inhibitor of catechol-O-methyltransferase activity reduces preterm birth and impedes cervical resistance to stretch in pregnant rats

Catechol-O-methyltransferase (COMT) enzyme catalyzes the methylation of the 2- or 4-hydroxyestrogens to 2- or 4-methoxyestrogens. Both the hydroxyestrogens and methoxyestrogens have been shown to block or enhance the effects of estrogen respectively. Our objective was to investigate the potential role of COMT in parturition and cervical ripening using a rat model. Immunohistochemistry was conducted to detect and localize the COMT protein in rat uterine tissues during pregnancy. We measured the longitudinal changes in urinary 2-hydroxyestrogen before, during, and after pregnancy in rats. Animal studies were conducted to determine the effect of treatment with a selective COMT inhibitor on (1) mifepristone-induced preterm birth and (2) cervical resistance to stretch in pregnant rats. The intensity of staining for the COMT protein differed within the luminal epithelium, uterine gland epithelium, endometrium, and myometrium during pregnancy. Levels of staining for the COMT protein in rat myometrium were highest on day 1 and lowest on days 8 and 13, but high levels returned by days 16 and 19 of pregnancy. The levels of urinary 2-hydroxyestrogen gradually increased in the first 2 weeks of pregnancy, peaked from days 16 to 18 of pregnancy, and then gradually returned to pre-pregnancy levels after delivery. The percentage of pups retained in the uterus of pregnant rats treated with both mifepristone and COMT inhibitor (48 +/- 15%) was significantly higher (P < 0.05) when compared with the value of pregnant rats treated with mifepristone alone (12 +/- 4%). The resistance to stretch was significantly higher (P < 0.05) in cervical tissues from the pregnant rats treated with COMT inhibitor (0.28) when compared with cervical tissues taken from rats treated with vehicle control (0.18). Modulation of COMT activity may play a role in the regulation of myometrial contractility and cervical ripening during pregnancy.

Serum soluble Fas in the syndrome of hemolysis, elevated liver enzymes, and low platelets

OBJECTIVE To assess whether serum levels of soluble Fas and soluble Fas ligand are altered in the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). METHODS Serum samples from 22 pregnant women diagnosed with HELLP syndrome were compared with sera from 37 healthy women with noncomplicated singleton pregnancies. Serum levels of soluble Fas and soluble Fas ligands were determined by enzyme immunoassay. Student t, χ2, Pearsons correlation coefficient, and multiple regression tests were used for statistical analyses. RESULTS Both soluble Fas and soluble Fas ligand were detected in the sera of normal pregnancies as well as in those with HELLP syndrome. The mean serum level of soluble Fas was significantly higher in women with HELLP syndrome than in healthy gravidas (10.75 ± 0.93 versus 5.81 ± 0.37 U/mL, P < .001). However, there was no significant difference in mean serum soluble Fas ligand levels of the two groups (0.60 ± 0.06 compared with 0.50 ± 0.22 ng/mL, P = .23). In women with HELLP syndrome, there were no significant correlations between serum levels of soluble Fas or soluble Fas ligand with liver transaminases (aspartate and alanine aminotransferase) and platelet count. CONCLUSION Serum levels of soluble Fas, but not soluble Fas ligand, are significantly higher in women with HELLP syndrome than healthy gravidas. The source of elevated serum levels of soluble Fas in HELLP syndrome remains to be determined

Disseminated Intravascular Coagulation, Hemoperitoneum, and Reversible Ischemic Neurological Deficit Complicating Anaphylaxis to Prophylactic Antibiotics during Cesarean Delivery: A Case Report and Review of Literature

Routine use of prophylactic antibiotics reduces the risk of postcesarean fever and infections by over 50% in both nonelective and elective (scheduled) procedures. Although anaphylaxis to prophylactic antibiotics is rare, potentially fatal complications might occur. Herein, we present a case where disseminated intravascular coagulation and reversible ischemic neurological deficit complicated anaphylactic reactions to prophylactic antibiotics administered during cesarean delivery. A 27-year-old gravida 9, para 7 at 392/7 weeks underwent elective repeat cesarean delivery and bilateral tubal ligation. Her surgery was complicated by intraoperative hypotension, generalized itching, and urticarial skin rash consistent with anaphylactic reaction upon administering prophylactic cefazolin. In the recovery room, she continued to be hemodynamically unstable despite energetic resuscitation. Hemoperitoneum was suspected, and laboratory evaluation indicated disseminated intravascular coagulation. Abdominal exploration revealed massive hemoperitoneum, but there was no source of active bleeding noted. The postoperative course was complicated by reversible ischemic neurological deficit, which resolved on expectant management. Disseminated intravascular coagulation and reversible ischemic neurological deficit may complicate anaphylactic reaction to prophylactic antibiotics administered during cesarean delivery. Immediate recognition and intervention is crucial for a successful outcome.

Conservative Management and Planned Surgery for Periviable Advanced Extrauterine Abdominal Pregnancy with Favorable Outcome: Report of Two Cases

Advanced abdominal pregnancy is an extremely rare condition that poses diagnostic and management challenges. A high index of suspicion and careful assessment of the patients symptoms, supplemented with obstetric ultrasound, and magnetic resonance imaging, are crucial for timely diagnosis and management to prevent life-threatening complications. The presence of periviable fetuses in advanced abdominal pregnancies increases the challenge to achieve a balance between maternal and fetal benefits and risks. Early diagnosis and management decisions via a multidisciplinary approach and planned delivery are of paramount importance to minimize complications and achieve favorable maternal and fetal outcomes. Even in the setting of oligohydramnios and suspected preterm premature rupture of membranes, in-patient conservative management and an individualized planned surgical approach that includes removing or leaving the placenta in place are appropriate for managing the periviable abdominal pregnancy.

Perinatal Outcomes after Short versus Prolonged Indomethacin for Tocolysis in Women with Preterm Labor

Objective Indomethacin tocolysis is generally limited to 48 hours. Indomethacin has been administered for longer durations to prolong gestation in extreme prematurity. Our aim is to compare perinatal outcomes after a prolonged course, > 48 hours versus ≤  48 hours in preterm labor. Methods A retrospective chart review of women admitted with preterm labor < 32 weeks gestation who received indomethacin for tocolysis. The primary maternal outcome was latency from admission until delivery. The primary neonatal outcome was a composite of severe neonatal morbidities. Results A total of 73 women were included: 32 (43.8%) received indomethacin for > 48 hours (prolonged) and 41 (56.2%) for ≤ 48 hours (standard). Prolonged group started on indomethacin at an earlier gestational age compared with standard group (23.9 [23.1-27.3] vs. 25.7 [23.8-28.5] weeks, p = 0.03). Latency from admission until delivery was longer in the prolonged group versus the standard group (1.8 [1.1-3] vs. 0.4 [0.1-0.8] weeks, p < 0.001). Prolonged use was not associated with increased risk of the composite neonatal outcome; however, there was a trend for more necrotizing enterocolitis. Conclusion A prolonged course of indomethacin may be an option for women with preterm labor at risk of extreme prematurity; it may also be associated with higher risks of some adverse neonatal outcomes.