Correlation between neonatal outcomes of twins depends on the outcome: secondary analysis of twelve randomised controlled trials.

OBJECTIVE: To estimate the magnitude of the correlation between neonatal outcomes of twins and demonstrate how this information can be used in the design of randomised controlled trials (RCTs) in women with twin pregnancies. DESIGN: Secondary analysis of data from 12 RCTs. SETTING: Obstetric care in multiple countries, 2004-2012. POPULATION OR SAMPLE: 4504 twin pairs born to women who participated in RCTs to assess treatments given during pregnancy. METHODS: Intraclass correlation coefficients (ICCs) were estimated using log-binomial and linear models. MAIN OUTCOME MEASURES: Perinatal death, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular haemorrhage, necrotising enterocolitis, sepsis, neonatal intensive care unit admission, birthweight, low birthweight and two composite measures of adverse neonatal outcome. RESULTS: ICCs for the composite measures of adverse neonatal outcome were all above 0.5, indicating moderate to strong correlation between adverse outcomes of twins. For individual neonatal outcomes, median ICCs across trials ranged from 0.13 to 0.79 depending on the outcome. An example illustrates how ICCs can be used in sample size calculations for RCTs in women with twin pregnancies. CONCLUSIONS: The correlation between neonatal outcomes of twins varies considerably between outcomes and may be lower than expected. Our ICC estimates can be used for designing and analysing RCTs that recruit women with twin pregnancies and for performing meta-analyses that include such RCTs. Researchers are encouraged to report ICCs for neonatal outcomes in twins in their own RCTs. TWEETABLE ABSTRACT: Correlation between neonatal outcomes of twins depends on the outcome and may be lower than expected.

A randomised controlled double-blind clinical trial of 17-hydroxyprogesterone caproate for the prevention of preterm birth in twin gestation (PROGESTWIN): evidence for reduced neonatal morbidity.

OBJECTIVE: To determine whether 17 alpha-hydroxyprogesterone caproate (17OHPC) prolongs gestation beyond 37 weeks of gestation (primary outcome) and reduces neonatal morbidity (secondary outcome) in twin pregnancy. DESIGN: Randomised controlled double-blind clinical trial. SETTING: Tertiary-care university medical centre. POPULATION: Unselected women with twin pregnancies. METHODS: Participants received weekly injections of 250 mg 17OHPC (n = 194) or placebo (n = 94), from 16-20 to 36 weeks of gestation. Randomisation was performed using the permuted-block randomisation method. Data were analysed on an intention-to-treat basis. MAIN OUTCOME MEASURE: Preterm birth (PTB) rate before 37 weeks of gestation. RESULTS: There were no significant differences in the average gestational age at delivery, or in the rates of PTB before 37, 32, and 28 weeks of gestation, between the two groups. The proportion of very-low-birthweight neonates (<1500 g) was significantly lower in the 17OHPC group (7.6%) compared with placebo (14.3%) (relative risk, RR 0.5; 95% confidence interval, 95% CI 0.3-0.9; P = 0.01). Progestogen-treated neonates had a significantly lower composite neonatal morbidity (19.1%) compared with placebo (30.9%) (odds ratio, OR 0.53; 95% CI 0.31-0.90; P = 0.02), with significantly lower odds for respiratory distress syndrome (14.4 versus 23.4%; OR 0.55; 95% CI 0.31-0.98; P = 0.04), retinopathy of prematurity (1.1 versus 4.6%; OR 0.21; 95% CI 0.05-0.96; P = 0.04), and culture-confirmed sepsis (3.4 versus 12.8%; OR 0.24; 95% CI 0.10-0.57; P = 0.00). CONCLUSIONS: Intramuscular 17OHPC therapy did not reduce PTB before 37 weeks of gestation in unselected twin pregnancies. Nonetheless, 17OHPC significantly reduced neonatal morbidity parameters and increased birthweight.

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis.

BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB). OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA). SEARCH STRATEGY: We searched international scientific databases, trial registration websites, and references of identified articles. SELECTION CRITERIA: Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB. MAIN RESULTS: Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75). AUTHOR'S CONCLUSIONS: In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.

The effect of maternal fasting during Ramadan on preterm delivery: a prospective cohort study.

OBJECTIVE: To determine the effect of fasting during the month of Ramadan on the rate of preterm delivery (PTD). DESIGN: A prospective cohort study of women with singleton pregnancies who elected to fast and matched controls. SETTING: Four medical centres in Beirut, Lebanon. POPULATION: Women presenting for prenatal care (20-34 weeks of gestation) during the month of Ramadan, September 2008. METHODS: Data were collected prospectively. The frequency of PTD was evaluated in relation to the duration of fasting and the stage of gestation at the time of fasting. MAIN OUTCOME MEASURES: The primary endpoint was the percentage of pregnant women who had PTD, defined as delivery before 37 completed weeks of gestation. RESULTS: A total of 468 women were approached, of whom 402 were included in the study. There were no differences in smoking history and employment. There was no difference in the proportion of women who had PTD at <37 weeks (10.4% versus 10.4%) or PTD at <32 weeks (1.5% versus 0.5%) in the Ramadan-fasted group and the controls, respectively. The PTD rate was also similar in those who fasted before or during the third trimester. The mean birthweight was lower (3094 ± 467 g versus 3202 ± 473 g, P = 0.024) and the rate of ketosis and ketonuria was higher in the Ramadan-fasted women. On multivariate stepwise logistic regression analysis, fasting was not associated with an increased risk of PTD (odds ratio 0.72; 95% confidence interval 0.34-1.54; P = 0.397). The only factor that had a significant effect on the PTD rate was body mass index (odds ratio 0.43; 95% confidence interval 0.20-0.93; P = 0.033). CONCLUSIONS: Fasting during the month of Ramadan does not seem to increase the baseline risk of preterm delivery in pregnant women regardless of the gestational age during which this practice is observed.

Episiotomy: history, present and future - a review.

Childbirth has always carried traumatic stress to the woman's body. To deliver with less perineal trauma, obstetricians have used episiotomies. Episiotomy is still a common practice despite the controversy regarding its use. Weighing the risks and benefits, the scientific literature supports its selective use. With the worldwide trend to reduce the rate of episiotomy, several techniques have been proposed to achieve that. However, further research is still needed to prove their efficacy. This review will shed light on the historical background of episiotomy, its different techniques, indications, and the future of its practice.

Plant growth promotion and biological control of Pythium aphanidermatum, a pathogen of cucumber, by endophytic actinomycetes.

AIMS: To evaluate the potential of Actinoplanes campanulatus, Micromonospora chalcea and Streptomyces spiralis endophytic in cucumber roots, to promote plant growth and to protect seedlings and mature plants of cucumber from diseases caused by Pythium aphanidermatum, under greenhouse conditions. METHODS AND RESULTS: Three endophytic isolates, out of 29, were selected through tests aimed at understanding their mechanisms of action as biocontrol agents and plant growth promoters. When applied individually or in combination, they significantly promoted plant growth and reduced damping-off and crown and root rot of cucumber. The combination of the three isolates resulted in significantly better suppression of diseases and plant growth promotion, than where the plants were exposed to individual strains. CONCLUSIONS: The three selected actinomycete isolates colonized cucumber roots endophytically for 8 weeks, promoted plant growth and suppressed pathogenic activities of P. aphanidermatum on seedling and mature cucumber plants. SIGNIFICANCE AND IMPACT OF THE STUDY: The results clearly show that the endophytic, glucanase-producing actinomycetes used, especially as a combined treatment, could replace metalaxyl, which is the currently recommended fungicide for Pythium diseases in the United Arab Emirates. These endophytic isolates also have the potential to perform as plant growth promoters, which is a useful attribute for crop production in nutrient impoverished soils.

C-reactive protein level as a predictor of difficult emergency laparoscopic cholecystectomy.

Background: Studies focused on C-reactive protein (CRP) as a marker of difficult laparoscopic cholecystectomy are limited to small case series. The aim of this study was to evaluate the association between preoperative CRP concentration and difficulty of laparoscopic cholecystectomy in patients admitted with a biliary emergency presentation. Methods: Patients with an emergency admission for biliary disease treated between 2012 and 2017 with a documented preoperative CRP level were analysed. Elective patients and those with other concurrent causes of increased CRP concentration were excluded. The intraoperative difficulty grade was based on the Nassar scale. Statistical analysis was conducted to determine the association of preoperative CRP level with difficulty grading, adjusted for the interval to surgery. Results: A total of 804 emergency patients were included. The mean preoperative peak CRP level was 64·7 mg/l for operative difficulty grade I, 69·6 mg/l for grade II, 98·2 mg/l for grade III, 217·5 mg/l for grade IV and 193·1 mg/l for grade V, indicating a significant association between CRP concentration and Nassar grade (P < 0·001). Receiver operating characteristic (ROC) curve analysis showed an area under the curve of 0·78 (95 per cent c.i. 0·75 to 0·82), differentiating patients with grade I-III from those with grade IV-V operative difficulty. ROC curve analysis found a cut-off CRP value of 90 mg/l, with 71·5 per cent sensitivity and 70·5 per cent specificity in predicting operative difficulty of grade IV or V. Logistic regression analysis found preoperative peak CRP level to be predictive of Nassar grade I-III versus grade IV-V operative difficulty, also when adjusted for timing of surgery (odds ratio 5·90, 95 per cent c.i. 2·80 to 12·50). Conclusion: Raised preoperative CRP levels are associated with greater operative difficulty based on Nassar scale grading.