Detailed statistical analysis plan for ALBINO: effect of Allopurinol in addition to hypothermia for hypoxic-ischemic Brain Injury on Neurocognitive Outcome - a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III).

BACKGROUND: Despite therapeutic hypothermia (TH) and neonatal intensive care, 45-50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants. Allopurinol - a xanthine oxidase inhibitor - reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult. This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE. METHODS/DESIGN: The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE. Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years. RESULTS: The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and ."will be stratified for the two treatment groups. DISCUSSION: The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT03162653. Registered on 22 May 2017.

Effect of nonconsecutive aerobic resistance training on blood glucose and childbirth outcome of women with gestational diabetes mellitus / 中国实用护理杂志

Objective:To investigate applications of nonconsecutive aerobic resistance training among women with gestational diabetes mellitus, to provide reference for pregnancy health care.Methods:The convenient sampling method was adopted, a total of 110 gestational diabetes mellitus pregnant women were selected who established card and regular obstetric check-up in Zhongshan City People's Hospital from June 2019 to June 2020 as the study subjects. They were divided into experimental group and control group according to the random number table method, each group contained 55 cases. Both groups were given routine pregnancy health care, based on this, the control group received aerobic walking for 6 times a week, and the experimental group was implemented nonconsecutive aerobic resistance training for 6 times a week. The fasting blood glucose and 2 h postprandial blood glucose levels of the two groups were compared at the time of enrollment, the 4th week, the 8th week and the 12th week of intervention, childbirth outcome was also compared between two groups.Results:At the 8th week and the 12th week of intervention, the levels of fasting blood glucose were (5.15 ± 0.48), (4.85 ± 0.37) mmol/L in the experimental group, lower than (5.36 ± 0.46), (5.18 ± 0.48) mmol/L in the control group; at the 4th, 8th and 12th week of intervention, 2 h postprandial blood glucose levels were (6.45 ± 0.52), (6.34 ± 0.44), (6.21 ± 0.40) mmol/L in the experimental group, lower than (6.73 ± 0.56), (6.74 ± 0.48), (6.49 ± 0.45) mmol/L in the control group, the difference was statistically significant ( t values were 2.19-4.30, P<0.05). The natural delivery rate in the experimental group was 85.7% (42/49), which was higher than 69.2% (36/52) in the control group; the incidence of perineal injury and respiratory distress were 12.2% (6/49) and 2.0% (1/49) in the experimental group, lower than 28.9% (15/52) and 15.4% (8/52) in the control group, the difference was statistically significant ( χ2 = 3.89, 4.22, P<0.05). Conclusions:Nonconsecutive aerobic resistance training can effectively control blood glucose, increase the natutal delivery rate and improve delivery outcomes of women with gestational diabetes mellitus.

Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO): study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III).

BACKGROUND: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. METHODS: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. DISCUSSION: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. TRIAL REGISTRATION: NCT03162653, www.ClinicalTrials.gov , May 22, 2017.

Effect of diazepam on maternal mood, cervical dilatation and childbirth outcome in the first stage of labor / 中国生化药物杂志

Objective To investigate the effect of diazepam injection on the degree of cervical dilatation, delivery outcome and negative emotion in the first stage of labor. Methods Retrospective study of 120 cases of maternal birth in our hospital as a study sample. Diazepam was used in the first stage of labor, and 60 cases of women with worse cervical dilatation and negative mood were selected as observation group, the other selected not to use any drug-assisted childbirth, only to take the basis of comfort and other interventions, the clinical symptoms and observation group were similar to 60 cases of maternal were classified as control group. The effects of the two groups intervention on maternal mood, delivery outcome and cervical dilatation were compared. Results The self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores of the observation group were significantly lower than those of the control group at 1h, 12h and 24h after treatment, the difference was statistically significant (P<0.05). Observation group Bishop cervix related degree of cervical dilatation, cervical soft and hard, cervix position, cervical canal disappearance and fetal exposure were significantly higher than those of the control group, the difference was statistically significant (P<0.05). The rate of spontaneous delivery in the observation group (83.33%) was significantly higher than that the control group (56.67%), the difference was statistically significant (P<0.05). There were no statistical differences in the rate of adverse childbirth in the observation group (11.67%) and the control group (10.00%). Conclusion The use of diazepam injection in the first stage of labor can effectively improve the overall maturity of maternal cervix, relieve maternal depression, anxiety and other negative psychological, and drug safety is high, and there was no significant adverse effect on the outcome of their childbirth.

Effect of dinoprostone suppositories and oxytocin in promoting cervical ripening and childbirth outcome / 中国生化药物杂志

Objective To explore the effect of dinoprostone suppositories and oxytocin on cervical maturation and delivery outcome in induction of labor in late pregnancy.Methods A total of 174 pregnant women in the department of obstetrics and gynecology in our hospital for treatment in late pregnancy were chosen.They were randomly divided into two groups: the control group 85 cases and the study group 89 cases.The control group was treated with routine induction of intravenous infusion of oxytocin, and the study group was taken with dinoprostone suppositories.The effective rates of induction of labor and the incidence of adverse reactions after induction of labor induced of the two groups were observed.The clinical effect of patients was with Bishop score to determine cervical maturity.The induction of labor time, natural childbirth rate, cesarean section rate, maternal postpartum hemorrhage and neonatal asphyxia score were as the evaluation criteria of childbirth outcome.Results The cervical maturation level was (7.26 ±1.82) after drug for 24 hours in the study group, significantly higher than that of the control group (6.34 ±1.37) (P<0.05).The induction time, spontaneous delivery rate and cesarean section rate of the study group were (6.34 ±1.37)h, 86.52%, 13.48%, significantly better than those in the control group (P<0.05).The average amount of bleeding in the study group was (225.96 ±12.81) mL and the neonatal asphyxia score was (9.73 ±0.15), the results were lower than the control group (P<0.05).The successful rate of induction of labor in the study group was 96.63%) higher than that in the control group 85.88%.The incidence of side effects in the study group was 10.11%, significantly lower than in the control group 21.18% (P<0.05), which were with statistical significance.Conclusion Dinoprostosterone suppositories have the advantage of promoting cervical ripening for late pregnancy in pregnant women compared with oxytocin.It can shorten induction time and improve natural childbirth rate.And the maternal prognosis is good, can be used as a safe and effective clinical induction.

Adverse obstetrical and perinatal outcome in adolescent mothers associated with first birth: a hospital-based case-control study in a tertiary care hospital in North-East India.

PURPOSE: To analyze the adverse obstetrical and perinatal outcome of adolescent mothers associated with first birth. PATIENTS AND METHODS: This prospective case-control study was conducted in a tertiary care teaching hospital of North-East India between January 2014 and December 2014. All adolescent primigravidae completing 28 weeks of gestation with singleton pregnancy and delivered at our institution were included in the study group. Primigravidae aged between 20 and 25 years were taken as a control group. Mothers having pregnancy complicated with diabetes mellitus, renal disorder, thyroid disorders, and cardiac diseases were excluded from the study. Demographic data, maternal complications like severe anemia, pre-eclampsia, eclampsia, gestational age at delivery, mode of delivery, and postpartum complications were compared. Among fetal complications, low-birth weight, preterm birth, neonatal intensive care unit admission, still birth, and early neonatal death were compared. All the patients were interviewed regarding contraceptive knowledge and its use preceding the pregnancy. RESULTS: Quality antenatal care was received by 80.6% of adolescent mothers. The adolescent mothers had a higher incidence of pre-eclampsia (odds ratio [OR] 2.017 95% confidence interval [CI]: 1.045-3.894, P=0.03), preterm deliveries (OR: 1.655, 95% CI: 1.039-2.636, P=0.03). Among fetal outcomes, the low- birth weight babies (OR: 1.59, 95% CI: 1.016-2.478), low mean birth weight (2,544.4±622.09 g versus 2,701.6±582.51 g), and higher admission to neonatal intensive care unit (OR: 1.957, 95% CI: 1.120-3.417) were significantly associated with adolescent mothers. There was no significant difference found regarding the mode of delivery, still birth, and early neonatal death. Moreover, contraceptive knowledge and its use were found to be poor among adolescent mothers. CONCLUSION: With quality antenatal, intranatal, and postnatal care, the obstetric risk of childbirth in adolescent mothers may not be as serious as perceived to be.