Measurement of maternal serum amyloid A as a novel marker of preterm birth.

OBJECTIVE: To study the association between maternal serum amyloid A (mSAA) levels and preterm birth (PTB). METHODS: This prospective observational nested case control study was conducted at Ain Shams University Maternity Hospital, Cairo, Egypt, between May 2017 and December 2017. The study recruited pregnant women at 26-34 weeks presented with threatened preterm labor (PTL). Women with PTB were included in cases group while control group included women who continued pregnancy and delivered at term. Serum samples were collected to measure mSAA levels. The main outcome of the study was the association between mSAA levels and PTB. Secondary outcomes included neonatal intensive care unit admissions and neonatal mortality. RESULTS: Fifty-eight women were included in the final analysis (29 in each group). Women with PTB had a statistically significant higher mSAA levels [5.1 (4.5-7.7) vs. 1.2 (0.0-2.5) mg/l, for cases and controls respectively, p < .001]. Higher mSAA levels were also observed among women whose babies were admitted to NICU, but there was no significant relation between mSAA level and neonatal death. A statistically significant negative correlation was found between mSAA and gestational age at delivery and neonatal birth weight. mSAA had an excellent value to predict PTB (AUC = 0.972 [95% CI, 0.891-0.998], p < .0001), fair value to predict admission to NICU and a poor value to predict neonatal death. CONCLUSIONS: mSAA level was found to be elevated among women with threatened PTL who end with PTB; mSAA is a potentially useful predictive marker of PTB that warrant further study. CLINICALTRIALS.GOV: NCT01639027.

Prediction of spontaneous preterm birth: salivary progesterone assay and transvaginal cervical length assessment after 24 weeks of gestation, another critical window of opportunity.

Objectives: Measurement of salivary progesterone (SP4) levels and cervical length (CL) after 24 weeks to assess their potential predictive value among asymptomatic women at high risk of spontaneous preterm birth (PTB). Methods: This prospective observational (noninterventional) study consecutively recruited asymptomatic women at high risk of spontaneous PTB. SP4 and CL were measured at recruitment (24-28 weeks of gestation) then repeated after 3-4 weeks. All recruited women were followed up regularly till delivery. The primary outcome measure was the occurrence of spontaneous PTB. Results: One hundred and thirty four women completed the study, 22 (16.4%) and 32 (23.9%) women had early (<34 weeks) and late (≥34 weeks) PTB, respectively. Initially, the mean CL was 3.2 ± 0.6 cm and the mean SP4 was 4062.8 ± 814.6 pg/ml; with follow up, the mean CL became 3.0 ± 0.6 cm and the mean SP4 became 3871.6 ± 1136.9. Women with early PTB had significantly lower initial and follow up CL and SP4 measures when compared to women with late PTB and those who had birth at term. The rate of drop in SP4 and CL measurements between the two visits was also significantly higher among women with early PTB than those with late PTB and term birth. Receiver-operating characteristic (ROC) curves showed that, CL was a good predictor but SP4 was a better predictor of PTB as the area under the curve (AUC) for CL was less than that for SP4 at both visits (i.e. 0.858 and 0.868 versus 0.986 and 0.990 at the initial and follow up visits, respectively). There was a statistically significant correlation between CL and SP4 measurements. Multivariable binary logistic regression analysis revealed that follow up SP4 measurement was the only independent predictor of spontaneous PTB, and neither BMI, maternal age, SP4 nor CL were independent predictors of early spontaneous PTB. Conclusions: After 24 gestational weeks, SP4 assessment is a simple and reliable promising tool to predict spontaneous PTB among asymptomatic high-risk women, with a little superior performance than CL measurement.

Pre-induction cervical ripening using two different dinoprostone vaginal preparations: A randomized clinical trial of tablets and slow release retrievable insert.

OBJECTIVE: The current study compared the safety and efficacy of two different dinoprostone preparations (dinoprostone vaginal tablets & dinoprostone slow release retrievable vaginal insert) to ripen the cervix at term. MATERIALS AND METHODS: Women admitted for pre-induction cervical ripening were included in a randomized controlled trial. Eligible women were randomly assigned to receive Dinoprostone either in the form of vaginal tablets or slow release retrievable vaginal insert. Study outcomes included time to vaginal delivery and time to onset of labor intervals and vaginal delivery rate. RESULTS: No statistically significant difference was found between the two groups regarding the main outcome measures, however, the probability of successful vaginal delivery was independently related to the type of dinoprostone preparation used to ripen the cervix (proportional hazard, 1.366; 95% CI, 1.010-1.847; P, 0.043) and the parity (proportional hazard, 1.412; 95% CI, 1.041-1.915; P, 0.026). CONCLUSION: Both dinoprostone preparations were effective and potentially safe. The probability of successful vaginal delivery was higher with dinoprostone vaginal tablets while use of dinoprostone vaginal insert was associated with better patients' acceptability. CLINICALTRIALS.GOV: NCT01635439.

Maternal serum amyloid A level as a novel marker of primary unexplained recurrent early pregnancy loss.

OBJECTIVE: To assess maternal serum amyloid A (SAA) levels among women with primary unexplained recurrent early pregnancy loss (REPL). METHODS: A prospective study was conducted among women with missed spontaneous abortion in the first trimester at Ain Shams University Maternity Hospital, Cairo, Egypt, between January 21 and December 25, 2014. Women with at least two consecutive primary unexplained REPLs and no previous live births were enrolled. A control group was formed of women with no history of REPL who had at least one previous uneventful pregnancy with no adverse outcomes. Serum samples were collected to measure SAA levels. The main outcome was the association between SAA and primary unexplained REPL. RESULTS: Each group contained 96 participants. Median SAA level was significantly higher among women with REPL (50.0 µg/mL, interquartile range 26.0-69.0) than among women in the control group (11.6 µg/mL, interquartile range 6.2-15.5; P<0.001). The SAA level was an independent indicator of primary unexplained REPL, after adjusting for maternal age and gestational age (odds ratio 1.12, 95% confidence interval 1.06-1.19; P<0.001). CONCLUSION: Elevated SAA levels found among women with primary unexplained REPL could represent a novel biomarker for this complication of pregnancy.

Blind vaginal fetal fibronectin swab for prediction of preterm birth.

AIM: To assess the accuracy of blind vaginal swab in diagnosis of preterm labor (PTL) and prediction of subsequent occurrence of preterm birth (PTB). METHODS: Eligible women who presented at 24-34 weeks of gestation with threatened PTL had their cervicovaginal secretions sequentially sampled for fetal fibronectin (fFN) using two types of swabbing techniques. The first swab was a blind vaginal swab collected without the aid of speculum, while the second one was a routine cervicovaginal swab. All participants were followed up until delivery. RESULTS: fFN in both swabs was significantly higher in women who delivered before term compared with women who delivered at term. On regression analysis, r(2) = 0.735 and 0.785 for blind vaginal and cervicovaginal swabs respectively, while on receiver operating characteristic analysis the area under curve was 0.965 and 0.977, respectively, without a statistically significant difference. Using an fFN cut-off of ≥0.05 µg/dL, the sensitivity, specificity, positive predictive value and negative predictive value of blind vaginal swab to predict PTB were 53.9%, 91.9%, 70.0% and 85.0%, respectively; while those for cervicovaginal swab were 58.3%, 94.7%, 77.8% and 87.8%, respectively. CONCLUSIONS: In women presenting at 24-34 weeks of gestation with threatened PTL, blind vaginal fFN swab is as effective as cervicovaginal swab to predict PTB, but it is easier to perform and does not require doctor supervision.

Can Porphyromonas gingivalis be a novel aetiology for recurrent miscarriage?

OBJECTIVE: To study the association between Porphyromonas gingivalis (P. gingivalis) infection and recurrent miscarriage. METHODS: This case control study included women with early pregnancy failure admitted for surgical evacuation of retained products of conception. Cases (group 1) included 50 women with unexplained recurrent early miscarriage whereas the control group (group 2) consisted of 50 women with no such history. The evacuated products of conception, subgingival plaques, cervicovaginal secretions and saliva of all participants were examined to detect P. gingivalis deoxyribonucleic acid (DNA) using a polymerase chain reaction. RESULTS: The prevalence of P. gingivalis DNA in the chorionic villous tissue samples of group 1 was significantly higher than in group 2 (8 [16%] vs. 1 [2%], respectively; p = 0.036, odds ratio [OR]: 9.3, 95% confidence interval [CI]: 1.1-76.9). The prevalence of P. gingivalis DNA was significantly higher in cervicovaginal secretions of group 1 than in group 2 (9 [18%] vs. 1 [2%], respectively; p = 0.02, OR: 10.8, 95% CI: 1.3-88.5). On the contrary, P. gingivalis DNA could not be detected in subgingival plaques and saliva samples of either group. CONCLUSION: The current study found an association between P. gingivalis infection of the female genital tract and the occurrence of recurrent miscarriage.

The association between pentraxin 3 in maternal circulation and pathological intrauterine fetal growth restriction.

OBJECTIVE: To assess the diagnostic accuracy of maternal serum pentraxin 3 (PTX3) in identifying pathological intrauterine fetal growth restriction (IUFGR) among women presented in the third trimester of pregnancy with a small for gestational age (SGA) fetus. STUDY DESIGN: This case control study was conducted in Ain-Shams University Maternity Hospital, Abbasiya Square, Cairo, Egypt and included women diagnosed at the third trimester of pregnancy as having a SGA fetus. Cases included pregnant women with pathological IUFGR, while women with physiologically SGA fetus were included in the control group. Diagnosis of antenatal SGA fetus was based on the presence of abdominal circumference <10th percentile. Pathological IUFGR was provisionally diagnosed antenatally by the presence of falling percentiles on serial ultrasound scans and then the definitive diagnosis was established postnatally after comprehensive neonatal evaluation. Maternal venous blood samples were collected from the eligible participants, once at the time of enrollment, to assess serum PTX3 levels using enzyme-linked immunosorbent assay (ELISA). Both groups were then followed up till delivery to confirm the diagnosis. RESULTS: Among the 68 pregnant included in the study, PTX3 was found to be significantly elevated in women with SGA fetus due to pathological IUFGR (n=34) than those with physiologically SGA fetus (n=34) [6.5 ng/ml (2.5-11.0) versus 1.2 ng/ml (0.8-2.5) respectively], with a best cutoff value of ≥1.3 ng/ml [sensitivity of 85.3% (95% confidence interval (CI), 68.9-95.0) and a specificity of 73.5% (95% CI, 55.6-87.1)]. Using multivariable binary logistic regression model, amniotic fluid index (AFI) (P=0.010), estimated fetal weight (EFW) (P=0.016), PTX3 level (P=0.041), and umbilical artery pulsatility index (UA-PI) (P=0.027) were all found to be independent diagnostic markers for pathological IUFGR. CONCLUSION: PTX3 is a promising marker that deserves further evaluation as it may differentiate normal and abnormal fetal growth among women presenting at third trimester of pregnancy with a SGA fetus.

Sacrospinous colpopexy using Masson luethy needle holder.

OBJECTIVE: Sacrospinous colpopexy (SSC) is a well-known surgical technique to correct apical support defect, however its approach is still challenging. The current study describes an alternative and economic approach for suture placement in the sacrospinous ligament during SSC using Masson luethy needle holder. STUDY DESIGN: A prospective study was conducted in a tertiary care center. The study recruited women with uterovaginal prolapse or post hysterectomy vaginal vault prolapse scheduled for SSC as a constructive surgery for vaginal superior segment defect. Eligible women were assigned to have SSC using Masson luethy needle holder (Group I) for suture placement in the sacrospinous ligament. The control group (Group II) consisted of a group of patients who had SSC using Deschamps ligature carrier. RESULTS: By the end of the study, 104 women underwent SSC. (Group I) included 55 women while (Group II) included 49 women. The mean SSC operative time was significantly shorter in (Group I) [109±33min versus 206±67min in (Group II), p<0001], with a mean difference of 10.5min [95% CI, 74-136]. This difference in SSC operative time was due to faster suture placement in (Group I) [47±14min versus 153±46min in (Group II), p<0001]. The mean SSC related operative blood loss was significantly less in (Group I) [582±349ml versus 985±463ml in (Group II), p<0001]. The perioperative complications, recurrence and cure rates were similar in both groups. CONCLUSION: Using Masson luethy needle holder reduced the difficulty associated with suture placement during SSC and allowed the completion of the procedure within a significantly shorter time.

Women with clomiphene citrate resistant polycystic ovarian disease: predictors of spontaneous ovulation after laparoscopic ovarian drilling.

OBJECTIVE: To evaluate the role of different clinical, biochemical and sonographic factors as predictors of spontaneous ovulation after laparoscopic ovarian drilling (LOD) in women with clomiphene citrate resistant polycystic ovarian disease (CCR-PCOD). STUDY DESIGN: This prospective study recruited 251 infertile women with CCR-PCOD. Several clinical, biochemical and sonographic criteria were tested as possible predictors of spontaneous ovulation after LOD using multivariate analysis. RESULTS: Women with higher preoperative levels of LH, FSH and/or androstenedione had significantly higher rates of spontaneous ovulation within the first eight weeks after LOD, but only FSH and androstenedione were found to be independent predictors. Other factors including age, BMI, type of infertility, duration of infertility, menstrual pattern, testosterone level, ovarian volume and SHBG were insignificant predictors. Receiver-operating characteristic (ROC) curves derived from FSH, LH, androstenedione, and a logistic regression model showed that the best cut-off values were 4.1IU/l, 7.8IU/l, 1.2ng/ml, and 0.4897, respectively, with sensitivity of 91.18%, 100%, 73.53%, and 88.24% and specificity of 69.57%, 69.57%, 65.22%, and 73.91% for FSH, LH, androstenedione, and logistic regression model respectively. An extended follow up (9 months after LOD) was conducted for the anovulatory and the non-pregnant ovulatory women, who were treated individually according to their clinical situation. Of these women, 53.5% (69/129) got pregnant, resulting in a cumulative pregnancy rate of 48% (82/171). Of these pregnancies, 16/82 (19.5%) were spontaneous while 35.4% (29/82) and 45.1% (37/82) occurred after ovulation induction by CC and gonadotropins, respectively. CONCLUSION: This study supports the use of androstenedione, LH and FSH as a simple reliable tool in triaging patients with CCR-PCOD to select the ideal candidates for LOD.

Drotaverine to improve progression of labor among nulliparous women.

OBJECTIVE: To reevaluate the role of the antispasmodic drug drotaverine in shortening the length of the active first stage of labor among nulliparous women. METHODS: In a randomized, double-blind, placebo-controlled trial, 422 young nulliparous women admitted to Ain-shams University Maternity Hospital, Cairo, Egypt, in spontaneous labor were initially enrolled between May and December 2012. Drotaverine hydrochloride (40mg) or placebo was given at the start of the active phase of labor and then repeated every 2hours (maximum 3 doses). All participants were consistently managed in accordance with the local institutional intrapartum protocol. The primary outcome was the rate of cervical dilation. RESULTS: After excluding women who delivered by cesarean, data were analyzed from 320 women. There was a significant difference in post-treatment labor pain scores, duration of the active phase of labor, and rate of cervical dilatation between the 2 groups (P<0.001 for all). There was no difference in maternal adverse effects. Kaplan-Meier survival analysis showed a greater probability of faster delivery among patients treated by drotaverine hydrochloride (log rank test; P<0.001). CONCLUSION: Drotaverine hydrochloride was used effectively and safely to shorten the duration of the first stage of labor among nulliparous women with active spontaneous labor. ClinicalTrials.gov: NCT01639027.

Skin test reactivity to female sex hormones in women with primary unexplained recurrent pregnancy loss.

The objective was to examine the hypothesis that primary unexplained recurrent pregnancy loss might be associated with an inappropriate immunologically mediated response to progesterone and/or estrogen. This prospective study included 47 women with two or more documented consecutive early pregnancy losses of unknown etiology, and no previous history of deliveries. Intradermal skin testing was performed in the luteal phase of the cycle (days 16-20) using estradiol benzoate, progesterone, and a placebo of refined sesame oil. Immediate (20 min) and late (24h and 1 week) skin test readings for all cases were compared with those of 12 parous women of comparable age with no history of spontaneous miscarriages, premenstrual disorders, pregnancy, or sex hormone-related allergic or autoimmune diseases. Main outcome measure was skin test reactivity to estradiol and/or progesterone. Immediate skin test reactivity to both hormones was observed among half of the cases at 20 min. A papule after 24h, which persisted for up to 1 week, was observed among 32 (68.1%) and 34 (72.3%) cases at the sites of estrogen and progesterone injection, respectively. 55.3% of cases had combined skin test reactivity to both estradiol and progesterone at 1 week. All women in the control group showed absence of skin test reactivity for both estradiol and progesterone at 20 min, 24h, and 1 week. None of the subjects in either group showed skin test reactivity to placebo. There is an association between primary unexplained recurrent pregnancy loss and skin test reactivity to female sex hormones.

Can a smaller than expected crown-rump length reliably predict the occurrence of subsequent miscarriage in a viable first trimester pregnancy?

AIM: To elicit the diagnostic value of smaller than expected crown-rump length (CRL) to predict the occurrence of subsequent miscarriage in women with a viable first trimester pregnancy. METHODS: A cohort study was conducted in the fetal special care unit of a tertiary care maternity hospital. The recruited participants were young pregnant women at 6-13 weeks of gestation. Transvaginal ultrasonography was performed to determine pregnancy viability and measure the embryonic CRL. To compare the differences in CRL between those pregnancies that remained viable and those that subsequently miscarried, the deviation of observed and expected CRL was calculated and expressed in standard deviations (SD) as Z score. The primary outcome measure was the percentage of pregnancies with antecedent growth delay that miscarried by the end of the first trimester. RESULTS: Of the pregnancies that subsequently miscarried, 79.3% (42/53) had smaller than expected CRL, and in 56.6% (30/53) the CRL was 2 SD or less from that expected for gestational age (GA). The mean Z score for CRL was significantly lower in pregnancies that subsequently miscarried compared to pregnancies that remained viable (-2.9 ± 2.6 vs -0.8 ± 2.1, respectively, P < 0.001). A CRL of 2 SD or less from that expected for GA as a cut-off point had a sensitivity of 56.6, specificity of 81.9, positive predictive value of 36.6, negative predictive value of 91.1, likelihood ratio positive of 3.1 and likelihood ratio negative of 0.5 in predicting subsequent miscarriage. CONCLUSION: Viable first trimester pregnancies with small for GA CRL were associated with a higher probability of a subsequent miscarriage.

Diagnostic validity of cervicovaginal human chorionic gonadotrophin at 26-36 weeks of gestation as a biochemical predictor of preterm birth.

AIM: The aim of this study was to assess the diagnostic accuracy of qualitative and quantitative assay of human chorionic gonadotrophin (hCG) in cervicovaginal secretion as a biochemical predictor of preterm birth. MATERIAL AND METHODS: A prospective study was conducted at Ain-Shams University Maternity Hospital, Cairo, Egypt. A total of 390 pregnant women were included in the statistical analysis: 90 women who presented with threatened preterm labor and 300 asymptomatic pregnant women with matched age, gestational age, bodyweight, parity and obstetric history. Qualitative and quantitative measurements of cervicovaginal fluid hCG at 26-36 weeks of gestation were performed to assess the risk for preterm birth. RESULTS: In women with threatened preterm labor (group 1) and asymptomatic pregnant women (group 2), preterm birth occurred in 35.6% and 9.3%, respectively. We analyzed predictive performances of qualitative and quantitative assay of hCG in cervicovaginal secretion, while combining group 1 and group 2. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of qualitative test, by the cut-off level of 25 mIU/mL, to predict preterm birth were 68.3%, 96.1%, 76.9%, 94.3% and 91.8%, respectively; those of quantitative test, by the cut-off level of 34.5 mIU/mL, were 100%, 98.5%, 92.3%, 100% and 98.7%, respectively. CONCLUSIONS: Both the qualitative and quantitative assessment of cervicovaginal fluid hCG at 26-36 weeks of gestation were valuable in the prediction of occurrence of preterm birth in the women who presented with threatened preterm labor as well as in the asymptomatic pregnant population.

Risk of postpartum uterine synechiae following uterine compression suturing during postpartum haemorrhage.

BACKGROUND: Uterine compression suturing is considered a successful, safe, inexpensive and simple method for the conservative treatment of atonic postpartum haemorrhage (PPH). However, insufficient data are available about the potential risk of subsequent intrauterine synechiae (IUS). AIM: To determine the risk of postpartum uterine synechiae in women who received isolated uterine compression suturing for the management of major uncontrolled PPH. MATERIALS & METHODS: All women with major PPH from May 2005 to June 2011 were reviewed retrospectively. Diagnostic hysteroscopy was performed to assess the uterine cavity in the 27 women who successfully underwent isolated uterine compression suturing for major atonic PPH and fulfilled the study inclusion and exclusion criteria. RESULTS: Among the 27 women who underwent isolated uterine compression suturing, 5 (18.5%) were found to have IUS on hysteroscopic examination. The mode of delivery for all women who developed IUS was caesarean section. Among these five women, three had mild IUS, one had moderate IUS and one had severe IUS. All adhesions were later successfully resected by hysteroscopy, except for one case with dense IUS. CONCLUSIONS: Uterine compression suturing was found to be associated with a risk of postpartum uterine synechiae formation, which may subsequently affect future fertility.