Effectiveness of pentoxifylline in severe early-onset fetal growth restriction: A randomized double-blinded clinical trial.

OBJECTIVE: Management of pregnancy complicated by severe early-onset fetal growth restriction (FGR) is one of the most challenging obstetrical issues. So far, there has not been a proven option for the treatment or improvement of this condition. Improper immune response during placentation leads to inadequate trophoblast invasion and impaired utero-placental perfusion. Pentoxifylline improves the endothelial function and induces vasodilation by reducing the inflammatory-mediated cytokines. We have evaluated the effect of Pentoxifylline on fetal-placental perfusion, neonatal outcome, and the level of oxidative stress markers before and after the intervention in the setting of severe early-onset FGR. MATERIALS AND METHODS: This study is a pilot randomized clinical trial on 40 pregnant women who had developed early-onset growth restricted fetus. Pentoxifylline and placebo were given with a dose of 400 mg per os two times daily until delivery. Serial ultrasound examination regarding fetal weight, amniotic fluid and also utero-placenta-fetal Doppler's were done. For the assessment of serum Antioxidant level, blood sampling was done once at the beginning of the study and again, at least, three weeks after the investigation. After delivery, umbilical-cord blood gas analysis, APGAR score at 1 and 5 min, NICU admission, and neonatal death were recorded and compared between the two groups. RESULTS: Utero-placenta-fetal Doppler's in the Pentoxifylline group did not significantly change compared to the control group. Fetal weight gain was significantly higher in the Pentoxifylline group before (996.33 ± 317.41) and after (1616.89 ± 527.90) treatment (P = 0.002). Total serum antioxidant capacity significantly increased in the Pentoxifylline group (p < 0.036). Average 5 min Apgar score was significantly higher (P < 0.036) and the percentage of babies admitted to NICU was significantly lower (P < 0.030) in the treated group. CONCLUSION: Using Pentoxifylline in pregnancy affected by FGR might show promising effects. In this study, Pentoxifylline improved the neonatal outcome, increased fetal weight gain, and reduced neonatal mortality by decreasing the level of oxidative stress markers and cutting down the inflammatory cascade.

Vaginal misoprostol and intravenous oxytocin for success of termination in the second-trimester intrauterine fetal demise: A randomized controlled clinical trial.

AIM: To compare the success rate of vaginal misoprostol versus intravenous (IV) oxytocin in termination of pregnancy in the second trimester intrauterine fetal death (IUFD). METHODS: This was an open-label randomized controlled study for 106 women with second trimester IUFD. Patients were randomly divided into two groups: women given vaginal misoprostol (400 mcg every 6 h up to 48 h) versus those given IV oxytocin (starting with 50 units up to a maximum of 300 units). When the first-line treatment (as mentioned above) failed, treatment methods were replaced with each other. When the second-line treatment failed, the patients underwent dilation and evacuation. RESULTS: The first-line treatment yielded the successful rate of 88.7% versus 73.7% for misoprostol versus oxytocin, respectively (p = 0.047). Among those with first-line treatment failure, the second-line treatment yielded success rate of 85.7% versus 83.3% for misoprostol versus oxytocin (p = 0.891). The mean duration of induction to delivery in women with successful response to first-line treatment was 28.72 and 20.55 h after initially receiving misoprostol versus oxytocin, respectively (p < 0.001). While during second-line treatment, this mean interval was not significantly different among those with misoprostol versus oxytocin (p = 0.128). No severe adverse events were observed. CONCLUSION: Vaginal misoprostol was associated with higher termination rate than oxytocin without adverse events when used as the first-line treatment. Both methods yielded the same success rate when used as the second-line treatment.

The use of vaginal progesterone as a maintenance therapy in women with arrested preterm labor: a double-blind placebo-randomized controlled trial.

BACKGROUND: The efficacy of maintenance tocolytic therapy after successful arrest of preterm labor remains controversial. The purpose of this study was to evaluate the efficacy of 400 mg of daily vaginal progesterone (cyclogest) after successful parenteral tocolysis to increase latency period and improvement of neonatal outcomes in women with threatened preterm labor. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled trial, 85 participants were randomly allocated to either 400 mg daily of vaginal progesterone (n = 45) or placebo (n = 40) until 34 weeks of gestation. The primary outcomes were the time until delivery (latency period) and cervical length after 1 week of treatment. Secondary outcome were GA on delivery, type of delivery, incidence of low birth weight, perinatal morbidity and mortality. RESULTS: Longer mean latency until delivery (53.6 ± 16.8 versus 34.5 ± 12.9) days p = .0001; longer mean of gestational age on delivery (37.5 ± 2.2 versus 34.2 ± 2.1) weeks p = .0001; cervical length after 1 week of treatment (27.5 ± 5.5 versus 20.7 ± 3.1) mm p = .0001; low birth weight 12 (29.3%) versus 19 (57.6%) p = .01; and NICU admission 9 (22%) versus 15 (45.5%), were significantly different between the two groups. No significant differences were found between neonatal death 1 (2.4%) versus 2 (6.1%), p = .43; RDS 5 (12.2%) versus 8 (24.2%), p = .17; and need to mechanical ventilator 2 (5.4%) versus 6 (18.2%) p = .136, for the progesterone and placebo groups, respectively. CONCLUSION: Daily administration of 400 mg vaginal progesterone after successful parenteral tocolysis may increase latency preceding delivery and improves cervical shortening and neonatal outcome in women with preterm labor. Further confirmatory studies are warranted.

A 5-year experience on perinatal outcome of placenta accreta spectrum disorder managed by cesarean hysterectomy in southern Iranian women.

BACKGROUND: We aimed to investigate the risk factors of placenta accreta spectrum (PAS) disorder, management options and maternal and neonatal outcomes of these pregnancies in a resource-limited clinical setting. METHODS: All women diagnosed with placenta accreta, increta, and percreta who underwent peripartum hysterectomy using a multidisciplinary approach in a tertiary center in Shiraz, southern Iran between January 2015 until October 2019 were included in this retrospective cohort study. Maternal variables, such as estimated blood loss, transfusion requirements and ICU admission, as well as neonatal variables such as, Apgar score, NICU admission and birthweight, were among the primary outcomes of this study. RESULTS: A total number of 198 pregnancies underwent peripartum hysterectomy due to PAS during the study period, of whom163 pregnancies had antenatal diagnosis of PAS. The mean gestational age at the time of diagnosis was 26 weeks, the mean intra-operative blood loss was 2446 ml, and an average of 2 packs of red blood cells were transfused intra-operatively. Fifteen percent of women had surgical complications with bladder injuries being the most common complication. Furthermore, 113 neonates of PAS group were admitted to NICU due to prematurity of which 15 (7.6%) died in neonatal period. CONCLUSION: Our findings showed that PAS pregnancies managed in a resource-limited setting in Southern Iran have both maternal and neonatal outcomes comparable to those in developed countries, which is hypothesized to be due to high rate of antenatal diagnosis (86.3%) and multidisciplinary approach used for the management of pregnancies with PAS.

The impact of betamethasone on fetal pulmonary, umbilical and middle cerebral artery Doppler velocimetry and its relationship with neonatal respiratory distress syndrome.

BACKGROUND: Prenatal corticosteroid administration is known to be an effective strategy in improving fetal pulmonary maturity. This study aimed to evaluate the impact of maternal betamethasone administration on fetal pulmonary and other arteries Doppler velocity and the correlation between RDS development and Doppler indices results. METHODS: Fifty one singleton pregnancies between 26 and 34 gestational weeks with a diagnosis of preterm labor were included in the exposed group and received betamethasone. Fifty one uncomplicated pregnancies were included in the non-exposed group. Fetal pulmonary, umbilical and middle cerebral arteries Doppler parameters were evaluated before and 24 to 48 h after steroid administration in the exposed group and two times at same intervals in the non-exposed group. Maternal records were matched to neonatal charts if delivery happened, and demographic and outcome data were abstracted. RESULTS: When compared with the nonexposed group, fetuses treated with corticosteroids demonstrated significantly decreased umbilical artery Pulsatility index (PI) and significantly increased the middle cerebral artery PI, pulmonary artery Acceleration time (AT) and pulmonary artery AT/ET (Ejection time), while all other indices remained similar. We found significantly decreased pulmonary artery AT in the fetuses with respiratory distress syndrome (RDS) compared to those that did not. CONCLUSIONS: The results of our study showed that maternal antenatal betamethasone administration caused significant changes in the fetus blood velocity waveforms and also affected the blood flow in the pulmonary artery which led to an increase in the pulmonary artery AT and AT/ET. Among those fetuses with RDS, we found a significant decrease in the pulmonary artery AT, but we did not observe any pulmonary artery AT/ET differences.

Episiotomy wound healing by Commiphora myrrha (Nees) Engl. and Boswellia carteri Birdw. in primiparous women: A randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Persian medicine manuscripts refer to plants such as Commiphora myrrha (Nees) Engl. (myrrh) and Boswellia carteri Birdw. (frankincense), which could be used to improve wound healing process. Since that time, local midwives in Iran continue to provide these herbs to precipitate episiotomy wound healing. AIM OF THE STUDY: To investigate the efficacy and safety of myrrh- and frankincense-based sitz-baths on episiotomy wound healing in primiparous women. MATERIALS AND METHODS: This randomized controlled trial was conducted on 90 primiparous women with singleton pregnancies after normal vaginal delivery at Hafez hospital affiliated to Shiraz University of Medical Sciences from July to October 2019. Study participants were randomly allocated in three groups (2 intervention groups and 1 control group). Women in intervention groups were assigned to receive either 10-min sitz-bath of myrrh extract or frankincense extract twice a day for 1 week. While the women in control group received the betadine sitz-bath for the same period of time. The main outcome was the episiotomy wound healing, which was measured using the REEDA scale before intervention, on 2nd and 7th postpartum days. RESULTS: An improvement in the episiotomy wound healing was significantly greater in patients receiving myrrh than those receiving the frankincense or betadine on 2nd (p = 0.003 and p < 0.001) and 7th (p = 0.043 and p = 0.015) postpartum days. However, the total REEDA score was not statistically different between the frankincense and betadine groups on 2nd and 7th postpartum days (p > 0.05). CONCLUSION: The present results suggest that myrrh was more efficient than frankincense and betadine in healing of the episiotomy wound and could be recommended as a safe natural therapy.

Obstetrics Healthcare Providers' Mental Health and Quality of Life During COVID-19 Pandemic: Multicenter Study from Eight Cities in Iran.

BACKGROUND: The coronavirus disease of 2019 (COVID-19) pandemic has become the most challenging issue for healthcare organizations and governments all over the world. The lack of evidence-based data on the management of COVID-19 infection during pregnancy causes an additional stress for obstetrics healthcare providers (HCPs). Therefore, this study was undertaken to evaluate depression, perceived social support, and quality of life among obstetrics HCPs. MATERIALS AND METHODS: This cross-sectional multicenter study was conducted in eight cities in Iran. During the study period, 599 HCPs were separated into direct, no direct, and unknown contact groups according to their exposure to COVID-19-infected pregnant patients. The Patient Health Questionaire-9 (PHQ-9), Multidimensional Scale of Perceived Social Support (MSPSS), and Short Form-36 (SF-36) were used to assess depression, perceived social support, and quality of life. RESULTS: Obstetrics and gynecology specialists had significantly higher social functioning and general health scores compared to other HCPs (residents/students or nurses/midwives). Depression was negatively correlated with most of the domains of quality of life, regardless of the COVID-19 contact status of the study participants. Social support, however, was positively correlated with some domains of quality of life, such as physical functioning, energy/fatigue, and emotional well-being, among staff members who had either direct contact or no contact with COVID-19 patients. CONCLUSION: During the COVID-19 outbreak, the depression score among obstetrics HCPs was negatively associated with quality of life. Social support, however, had a reinforcing effect on quality of life.

Effect of Acupuncture on Pregnancy-Related Insomnia and Melatonin: A Single-Blinded, Randomized, Placebo-Controlled Trial.

OBJECTIVE: The aim of the current study is to evaluate the efficacy and safety of acupuncture on sleep quality and overnight melatonin secretion, measured as urinary 6-sulfatoxymelatonin, in pregnant women. PATIENTS AND METHODS: This randomized, parallel, single-blinded (participant), controlled trial was conducted on 72 pregnant women with insomnia. Study participants were randomly assigned to either the intervention, 10 sessions of acupuncture treatment over a 3-week period, or control group by block randomization (1:1). Patients in both groups were evaluated at baseline and post-treatment (third week) using the Pittsburgh Sleep Quality Index (PSQI) score (as the primary outcome) and urinary 6-sulfatoxymelatonin. RESULTS: Fifty-five of 72 participants completed the study. There was no statistically significant difference regarding PSQI score and 6-sulfatoxymelatonin level between intervention and control groups at the baseline (P=0.169 and P=0.496). At the end of the study period, treatment with acupuncture significantly improved the PSQI score (P<0.001) with a large effect size of 3.7, as well as 6-sulfatoxymelatonin level (P=0.020) with a medium effect size of 0.6 as compared to the control group. No adverse effects were noted during acupuncture sessions and follow-up visits. CONCLUSION: Acupuncture was shown to significantly improve the sleep quality in pregnant women, possibly through increasing melatonin secretion, and could be recommended as a low-cost and low-risk alternative treatment to pharmacological therapies.

Efficacy and safety of myrrh in patients with incomplete abortion: a randomized, double-blind, placebo-controlled clinical study.

BACKGROUND: Myrrh (Commiphora myrrha (Nees) Engl.) has a long history of traditional use as a herbal medicine for different purposes. In ancient traditional Persian manuscripts, it has been noted that myrrh may act as uterine stimulant and probably cause complete abortion. However, there is no evidence to verify this comment. Therefore, the current study was carried out to evaluate the efficacy and safety of Myrrh in the treatment of incomplete abortion. MATERIALS AND METHODS: In a randomized double-blinded placebo controlled clinical trial, 80 patients with ultrasound-documented retained products of conception (RPOC) were assigned to receive capsules containing 500 mg of Myrrh oleo-gum-resin or a placebo three times a day for 2 weeks. The existence of the retained tissue and its size were evaluated by ultrasound examination at the beginning and end of the study. RESULTS: After 2 weeks, the mean diameter of the RPOC in the Myrrh group was significantly reduced compared with the placebo group (P < 0.001). Meanwhile, the rate of successful complete abortion was 82.9% in the intervention group and 54.3% in the placebo group (P = 0.01). The patients in both groups reported no serious drug-related adverse effects. CONCLUSION: This study shows that Myrrh is effective and safe in the resolution of the RPOC and may be considered as an alternative option for treatment of patients with incomplete abortion. However, further studies on active compounds isolated from myrrh and their uterine stimulant effects are needed. TRIAL REGISTRATION: This study was retrospectively registered at Iranian Registry of Clinical Trials (www.irct.ir) IRCT code: IRCT20140317017034N7.

Positive effect of low dose vitamin D supplementation on growth of fetal bones: A randomized prospective study.

The effect of vitamin D supplementation on growth of fetal bones during pregnancy is unclear. The aim of this study was to assess the effect of low dose vitamin D supplementation during pregnancy on bony anthropometric aspects of the fetus. In this prospective randomized trial, 140 patients were divided into two equally matched groups according to age, 25(OH)D level, exercise, and dietary intake. Then 1000 IU per day vitamin D supplement was given to the intervention group while the control group received placebo. Then crown-rump length (CRL) and femur length (FL) during the first trimester and humerus and femur lengths as well as their proximal metaphyseal diameter (PMD), midshaft diameter (MSD) and distal metaphyseal diameter (DMD) in the second and third trimester were measured using ultrasonography technique. Finally, no significant difference was observed for CRL (p = 0.93). Although FL was not statistically significant in the first trimester (p = 0.54), its measurement in the intervention group and the control group in the second (28.87 ±â€¯2.14 vs. 26.89 ±â€¯2.08; p ≤0.001) and the third (65.31 ±â€¯2.17 vs. 62.85 ±â€¯1.94; p ≤0.001) trimesters was significantly different. Femoral PMD, MSD, and DMD measurement increased more in the intervention group in comparison with the control group with P values <0.05. HL measurement in the intervention group and the control group in the second (28.62 ±â€¯1.94 vs. 27.23 ±â€¯2.08; p ≤0.001) and the third (61.29 ±â€¯2.84 vs. 59.85 ±â€¯1.79; p ≤0.001) trimesters revealed significant differences. Humeral PMD, MSD, and DMD measurement increased in the intervention group in comparison with the control group with P values <0.001 for all. It is suggested to prescribe low dose vitamin D (1000 IU per day) from early pregnancy with possible increment in length and diameter of femur and humerus bones of the fetus.

Double-blind randomized placebo-controlled trial on efficacy and safety of Lactuca sativa L. seeds on pregnancy-related insomnia.

ETHNOPHARMACOLOGICAL RELEVANCE: There is limited evidence about the role of herbal and traditional medicine in pregnancy-related insomnia. Extant documents on traditional Persian medicine refer to many plants which could induce sleep and which were used by pregnant women. In Iran, local herbal shops continue to provide these herbs to pregnant women to treat insomnia. One such herb is Lactuca sativa L. The aim of this study was to evaluate the effects of lettuce seed on pregnant women for the treatment of insomnia. METHODS AND MATERIALS: In a prospective randomized clinical trial, 100 pregnant women with insomnia aged 20-45 years were assigned to receive capsules containing 1000 mg of lettuce seed or a placebo daily for two weeks. The main outcome was the quality of sleep, which was measured using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Each group contained 50 participants. An improvement in the PSQI score was significantly greater in patients receiving lettuce seed than those receiving the placebo. Linear regression analysis showed that, after controlling for the other variables, the average sleep score of the experimental group was significantly lower than for the placebo group (p = 0.03). CONCLUSIONS: The findings of this study suggest that lettuce seed decreased insomnia during pregnancy and could be recommended as a safe natural remedy for treatment of pregnancy-related insomnia.

Evaluation of serum biomarkers for detection of preeclampsia severity in pregnant women.

OBJECTIVES: To determine serum biomarkers in detection of preeclampsia severity among pregnant women. METHODS: Among 450 pregnant women with various severity of preeclampsia, serum biomarkers ofaspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), hemoglobin (Hb), platelet count (PLT), uric acid, direct bilirubin, total bilirubin, creatinine, and alkaline phosphatase were compared using area under the Receiver operating characteristic (ROC) curve and Area Under the Curve (AUC). RESULTS: The mean age of women was 30.63±6.43 years and with mean gestational age of 34.69±3.97 weeks. The mean level of LDH, ALT, uric acid, and creatinine were significantly higher in the women with severe type of preeclampsia compared to those with mild type. LDH level had ROC and AUC of more than 0.80, with highest sensitivity, and moderatespecificityin comparison to other markers. CONCLUSION: Biomarkers such as ALT, uric acid, and LDH were shown to be prognostic in detection of theseverity of preeclampsia. LDH was demonstrated to significantly be a better prognostic test in detection of preeclampsia severity.