Royal Jubilee Maternity Services
Hospital / health systemBelfast, United Kingdom
Research output, citation impact, and the most-cited recent papers from Royal Jubilee Maternity Services (United Kingdom). Aggregated across the NobleBlocks index of 300M+ scholarly works.
Top-cited papers from Royal Jubilee Maternity Services
OBJECTIVE: To determine whether moderate hypothermia after hypoxic-ischaemic encephalopathy in neonates improves survival and neurological outcome at 18 months of age. DESIGN: A meta-analysis was performed using a fixed effect model. Risk ratios, risk difference, and number needed to treat, plus 95% confidence intervals, were measured. DATA SOURCES: Studies were identified from the Cochrane central register of controlled trials, the Oxford database of perinatal trials, PubMed, previous reviews, and abstracts. Review methods Reports that compared whole body cooling or selective head cooling with normal care in neonates with hypoxic-ischaemic encephalopathy and that included data on death or disability and on specific neurological outcomes of interest to patients and clinicians were selected. Results We found three trials, encompassing 767 infants, that included information on death and major neurodevelopmental disability after at least 18 months' follow-up. We also identified seven other trials with mortality information but no appropriate neurodevelopmental data. Therapeutic hypothermia significantly reduced the combined rate of death and severe disability in the three trials with 18 month outcomes (risk ratio 0.81, 95% confidence interval 0.71 to 0.93, P=0.002; risk difference -0.11, 95% CI -0.18 to -0.04), with a number needed to treat of nine (95% CI 5 to 25). Hypothermia increased survival with normal neurological function (risk ratio 1.53, 95% CI 1.22 to 1.93, P<0.001; risk difference 0.12, 95% CI 0.06 to 0.18), with a number needed to treat of eight (95% CI 5 to 17), and in survivors reduced the rates of severe disability (P=0.006), cerebral palsy (P=0.004), and mental and the psychomotor developmental index of less than 70 (P=0.01 and P=0.02, respectively). No significant interaction between severity of encephalopathy and treatment effect was detected. Mortality was significantly reduced when we assessed all 10 trials (1320 infants; relative risk 0.78, 95% CI 0.66 to 0.93, P=0.005; risk difference -0.07, 95% CI -0.12 to -0.02), with a number needed to treat of 14 (95% CI 8 to 47). CONCLUSIONS: In infants with hypoxic-ischaemic encephalopathy, moderate hypothermia is associated with a consistent reduction in death and neurological impairment at 18 months.
BACKGROUND: Diabetes mellitus (DM) is increasing in men of reproductive age. Despite this, the prevalence of diabetes in men attending fertility clinics is largely unknown. Furthermore, studies examining the effects of DM on sperm fertility potential have been limited to conventional semen analysis. METHODS: Conventional semen analysis (semen volume, sperm count, motility and morphology) was performed for 27 diabetic (mean age 34+/-2 years) and 29 non-diabetic subjects (control group, men undergoing routine infertility investigations, mean age 33+/-1 years). Nuclear DNA (nDNA) fragmentation was assessed using the alkaline Comet assay and mitochondrial DNA (mtDNA) deletions by Long-PCR. RESULTS: Other than a small, but significant, reduction in semen volume in diabetic men (2.6 versus 3.3 ml; P<0.05), conventional semen parameters did not differ significantly from control subjects. Diabetic subjects had significantly higher mean nDNA fragmentation (53 versus 32%; P<0.0001) and median number of mtDNA deletions (4 versus 3; P<0.05) compared with control subjects. CONCLUSIONS: Diabetes is associated with increased sperm nuclear and mtDNA damage that may impair the reproductive capability of these men.
BACKGROUND: The preferred timing of umbilical-cord clamping in preterm infants is unclear. METHODS: We randomly assigned fetuses from women who were expected to deliver before 30 weeks of gestation to either immediate clamping of the umbilical cord (≤10 seconds after delivery) or delayed clamping (≥60 seconds after delivery). The primary composite outcome was death or major morbidity (defined as severe brain injury on postnatal ultrasonography, severe retinopathy of prematurity, necrotizing enterocolitis, or late-onset sepsis) by 36 weeks of postmenstrual age. Analyses were performed on an intention-to-treat basis, accounting for multiple births. RESULTS: Of 1634 fetuses that underwent randomization, 1566 were born alive before 30 weeks of gestation; of these, 782 were assigned to immediate cord clamping and 784 to delayed cord clamping. The median time between delivery and cord clamping was 5 seconds and 60 seconds in the respective groups. Complete data on the primary outcome were available for 1497 infants (95.6%). There was no significant difference in the incidence of the primary outcome between infants assigned to delayed clamping (37.0%) and those assigned to immediate clamping (37.2%) (relative risk, 1.00; 95% confidence interval, 0.88 to 1.13; P=0.96). The mortality was 6.4% in the delayed-clamping group and 9.0% in the immediate-clamping group (P=0.03 in unadjusted analyses; P=0.39 after post hoc adjustment for multiple secondary outcomes). There were no significant differences between the two groups in the incidences of chronic lung disease or other major morbidities. CONCLUSIONS: Among preterm infants, delayed cord clamping did not result in a lower incidence of the combined outcome of death or major morbidity at 36 weeks of gestation than immediate cord clamping. (Funded by the Australian National Health and Medical Research Council [NHMRC] and the NHMRC Clinical Trials Centre; APTS Australian and New Zealand Clinical Trials Registry number, ACTRN12610000633088 .).
BACKGROUND: Chronic lung disease remains a major problem in neonatal intensive care units. Persistent inflammation in the lungs is the most likely underlying pathogenesis. Corticosteroids have been used to either prevent or treat chronic lung disease because of their potent anti-inflammatory effects. OBJECTIVES: To examine the relative benefits and adverse effects of postnatal corticosteroids commenced within the first seven days of life to preterm infants at risk of developing chronic lung disease. SEARCH METHODS: We sought randomised controlled trials (RCTs) of postnatal corticosteroid therapy from the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 8), MEDLINE (1966 to August 2013), handsearching paediatric and perinatal journals, and by examining previous review articles and information received from practising neonatologists. We contacted authors of all studies, where possible, to confirm details of reported follow-up studies, or to obtain any information about long-term follow-up where none had been reported. SELECTION CRITERIA: We selected RCTs of postnatal corticosteroid treatment within the first seven days of life (early) in high-risk preterm infants for this review. Most studies evaluated the use of dexamethasone but we also included studies that assessed hydrocortisone, even if it was used primarily to manage hypotension. DATA COLLECTION AND ANALYSIS: We extracted and analysed data regarding clinical outcomes that included mortality, chronic lung disease, death or chronic lung disease, failure to extubate, complications during the primary hospitalisation, and long-term health outcomes. MAIN RESULTS: Twenty-nine RCTs enrolling a total of 3750 participants were eligible for inclusion in this review. The overall risk for bias was probably low as all were randomised controlled trials, and most trials have used rigorous methods. There were significant benefits for the following outcomes: lower rates of failure to extubate and decreased risks of chronic lung disease at both 28 days and 36 weeks' postmenstrual age, death or chronic lung disease at 28 days and 36 weeks' postmenstrual age, patent ductus arteriosus and ROP, including severe ROP. There were no significant differences in the rates of neonatal or subsequent mortality, infection, severe intraventricular haemorrhage, periventricular leukomalacia, necrotising enterocolitis or pulmonary haemorrhage. Gastrointestinal bleeding and intestinal perforation were important adverse effects. The risks of hyperglycaemia, hypertension, hypertrophic cardiomyopathy and growth failure were also increased. In the 12 trials that reported late outcomes, several adverse neurological effects were found at follow-up examinations, including developmental delay (not defined), cerebral palsy and abnormal neurological examination. However, major neurosensory disability was not significantly increased, either overall in the seven studies where this outcome could be determined, or in the two individual studies where the rates of cerebral palsy or abnormal neurological examination were significantly increased. Moreover, the rates of the combined outcomes of death or cerebral palsy, or of death or major neurosensory disability, were not significantly increased. Dexamethasone was used in most studies (n = 20); only nine studies used hydrocortisone. In subgroup analyses by type of corticosteroid, most of the beneficial and harmful effects were attributable to dexamethasone; hydrocortisone had little effect on any outcomes except for an increase in intestinal perforation and a borderline reduction in patent ductus arteriosus. AUTHORS' CONCLUSIONS: The benefits of early postnatal corticosteroid treatment (≤ 7 days), particularly dexamethasone, may not outweigh the adverse effects of this treatment. Although early corticosteroid treatment facilitates extubation and reduces the risk of chronic lung disease and patent ductus arteriosus, it causes short-term adverse effects including gastrointestinal bleeding, intestinal perforation, hyperglycaemia, hypertension, hypertrophic cardiomyopathy and growth failure. Long-term follow-up studies report an increased risk of abnormal neurological examination and cerebral palsy. However, the methodological quality of the studies determining long-term outcomes is limited in some cases; the surviving children have been assessed predominantly before school age, and no study has been sufficiently powered to detect important adverse long-term neurosensory outcomes. There is a compelling need for the long-term follow-up and reporting of late outcomes, especially neurological and developmental outcomes, among surviving infants who participated in all randomised trials of early postnatal corticosteroid treatment. Hydrocortisone in the doses and regimens used in the reported RCTs has few beneficial or harmful effects and cannot be recommended for the prevention of chronic lung disease.
Background \n \nPolycystic ovary syndrome (PCOS) is characterised by infrequent or absent ovulation, and high levels of androgens and insulin (hyperinsulinaemia). Hyperinsulinaemia occurs secondary to insulin resistance and is associated with increased risk of cardiovascular disease and diabetes mellitus. Insulin‐sensitising agents such as metformin may be effective in treating PCOS‐related anovulation. \n \nObjectives \n \nTo evaluate the effectiveness and safety of insulin‐sensitising drugs in improving reproductive and metabolic outcomes for women with PCOS undergoing ovulation induction. \n \nSearch methods \n \nWe searched the following databases from inception to January 2017: Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL. We searched registers of ongoing trials and reference lists from relevant studies. \n \nSelection criteria \n \nWe included randomised controlled trials of insulin‐sensitising drugs compared with placebo, no treatment, or an ovulation‐induction agent for women with oligo and anovulatory PCOS. \n \nData collection and analysis \n \nTwo review authors independently assessed studies for eligibility and bias. Primary outcomes were live birth rate and gastrointestinal adverse effects. Secondary outcomes included other pregnancy outcomes, menstrual frequency and metabolic effects. We combined data to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I2 statistic and reported quality of the evidence for primary outcomes using GRADE methodology. \n \nMain results \n \nWe assessed the interventions metformin, clomiphene citrate, metformin plus clomiphene citrate, D‐chiro‐inositol, rosiglitazone and pioglitazone. We compared these with each other, placebo or no treatment. We included 48 studies (4451 women), 42 of which investigated metformin (4024 women). Evidence quality ranged from very low to moderate. Limitations were risk of bias (poor reporting of methodology and incomplete outcome data), imprecision and inconsistency. \n \nMetformin versus placebo or no treatment \n \nThe evidence suggests that metformin may improve live birth rates compared with placebo (OR 1.59, 95% CI 1.00 to 2.51, 4 studies, 435 women, I2 = 0%, low‐quality evidence). The metformin group experienced more gastrointestinal side effects (OR 4.76, 95% CI 3.06 to 7.41, 7 studies, 670 women, I2 = 61%, moderate‐quality evidence) but had higher rates of clinical pregnancy (OR 1.93, 95% CI 1.42 to 2.64, 9 studies, 1027 women, I2 = 43%, moderate‐quality evidence), ovulation (OR 2.55, 95% CI 1.81 to 3.59, 14 studies, 701 women, I2 = 58%, moderate‐quality evidence) and menstrual frequency (OR 1.72, 95% CI 1.14 to 2.61, 7 studies, 427 women, I2 = 54%, low‐quality evidence). There was no clear evidence of a difference in miscarriage rates (OR 1.08, 95% CI 0.50 to 2.35, 4 studies, 748 women, I2 = 0%, low‐quality evidence). \n \nMetformin plus clomiphene citrate versus clomiphene citrate alone \n \nThere was no conclusive evidence of a difference between the groups in live birth rates (OR 1.21, 95% CI 0.92 to 1.59, 9 studies, 1079 women, I2 = 20%, low‐quality evidence), but gastrointestinal side effects were more common with combined therapy (OR 3.97, 95% CI 2.59 to 6.08, 3 studies, 591 women, I2 = 47%, moderate‐quality evidence). However, the combined therapy group had higher rates of clinical pregnancy (OR 1.59, 95% CI 1.27 to 1.99, 16 studies, 1529 women, I2 = 33%, moderate‐quality evidence) and ovulation (OR 1.57, 95% CI 1.28 to 1.92, 21 studies, 1624 women, I2 = 64%, moderate‐quality evidence). There was a statistically significant difference in miscarriage rate per woman, with higher rates in the combined therapy group (OR 1.59, 95% CI 1.03 to 2.46, 9 studies, 1096 women, I2 = 0%, low‐quality evidence) but this is of uncertain clinical significance due to low‐quality evidence, and no clear difference between groups when we analysed miscarriage per pregnancy (OR 1.30, 95% CI 0.80 to 2.12, 8 studies; 400 pregnancies, I2 = 0%, low‐quality evidence). \n \nMetformin versus clomiphene citrate \n \nWhen all studies were combined, findings for live birth were inconclusive and inconsistent (OR 0.71, 95% CI 0.49 to 1.01, 5 studies, 741 women, I2 = 86%, very low‐quality evidence). In subgroup analysis by obesity status, obese women had a lower birth rate in the metformin group (OR 0.30, 95% CI 0.17 to 0.52, 2 studies, 500 women, I2 = 0%, very low‐quality evidence), while data from the non‐obese group showed a possible benefit from metformin, with high heterogeneity (OR 1.71, 95% CI 1.00 to 2.94, 3 studies, 241 women, I2 = 78%, very low‐quality evidence). Similarly, among obese women taking metformin there were lower rates of clinical pregnancy (OR 0.34, 95% CI 0.21 to 0.55, 2 studies, 500 women, I2 = 0%, very low‐quality evidence) and ovulation (OR 0.29, 95% CI 0.20 to 0.43 2 studies, 500 women, I2 = 0%, low‐quality evidence) while among non‐obese women, the metformin group had more pregnancies (OR 1.56, 95% CI 1.05 to 2.33, 5 studies, 490 women, I2 = 41%, very low‐quality evidence) and no clear difference in ovulation rates (OR 0.81, 95% CI 0.51 to 1.28, 4 studies, 312 women, low‐quality evidence, I2=0%). There was no clear evidence of a difference in miscarriage rates (overall: OR 0.92, 95% CI 0.50 to 1.67, 5 studies, 741 women, I2 = 52%, very low‐quality evidence). \n \nD‐chiro‐inositol (2 studies), rosiglitazone (1 study) or pioglitazone (1 study) versus placebo or no treatment \n \nWe were unable to draw conclusions regarding other insulin‐sensitising drugs as no studies reported primary outcomes.
BACKGROUND: Corticosteroids have been used late in the neonatal period to treat chronic lung disease (CLD) in preterm babies, and early to try to prevent it. CLD is likely to be the result of persisting inflammation in the lung and the use of powerful anti-inflammatory drugs like dexamethasone has some rationale. Early use tends to be associated with increased adverse effects so that studies of moderately early treatment (7-14 days postnatal) might have the dual benefits of fewer side effects and onset of action before chronic inflammation is established. OBJECTIVES: To determine if moderately early (7-14 days) postnatal corticosteroid treatment vs control (placebo or nothing) is of benefit in the prevention and/or treatment of early chronic lung disease in the preterm infant. SEARCH STRATEGY: Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, Cochrane Database of Controlled Trials, MEDLINE (1966 - October 2002), hand searching paediatric and perinatal journals, examining previous review articles and information received from practicing neonatologists. Authors of all studies were contacted, where possible, to confirm details of reported follow-up studies, or to obtain any information about long-term follow-up where none had been reported. SELECTION CRITERIA: Randomised controlled trials of postnatal corticosteroid treatment from 7-14 days of birth in high risk preterm infants were selected for this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality, CLD (including late rescue with corticosteroids, or need for home oxygen therapy), death or CLD, failure to extubate, complications during the primary hospitalisation (including infection, hyperglycaemia, hypertension, hypertrophic cardiomyopathy, pneumothorax, severe intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC), gastrointestinal bleeding, and severe retinopathy of prematurity (ROP)), and long term outcome (including blindness, deafness, cerebral palsy and major neurosensory disability), were abstracted and analysed using RevMan 4.1. MAIN RESULTS: Seven studies enrolling a total of 669 participants were eligible for inclusion in this review. Moderately early steroid treatment (vs placebo or nothing) reduced mortality by 28 days, chronic lung disease at 28 days and 36 weeks, and death or chronic lung disease at 28 days or 36 weeks. Earlier extubation was facilitated. There was no significant effect on the rates of pneumothorax, severe ROP, or NEC. Adverse effects included hypertension, hyperglycaemia, gastrointestinal bleeding, hypertrophic cardiomyopathy and infection. Steroid-treated infants were less likely to need late rescue with dexamethasone. There were limited data from four studies of long term follow-up; these did not show evidence of an increase in adverse neurological outcomes. REVIEWER'S CONCLUSIONS: Moderately early corticosteroid therapy (started at 7-14 days) reduces neonatal mortality and CLD, but at the cost of important short term adverse effects. Limited evidence concerning long term effects is provided by the trials included in this review. The methodological quality of the studies determining the long-term outcome is limited in some cases, the children have been assessed predominantly before school age, and no study has been sufficiently powered to detect important adverse long-term neurosensory outcomes. Therefore, given the risk:benefit ratio of short-term effects and the limited long-term follow-up data, it seems appropriate to reserve moderately early corticosteroid treatment to infants who cannot be weaned from mechanical ventilation and to minimise the dose and duration of any course of therapy. More research is urgently needed, including long term follow-up of survivors included in previous and any future trials, before the benefits and risks of postnatal steroid treatment, including initiation at 7-14 days, can be reliably assessed (See DART study; Doyle 2000a).
BACKGROUND: Sperm DNA damage shows great promise as a biomarker of infertility. The study aim is to determine the usefulness of DNA fragmentation (DF), including modified bases (MB), to predict assisted reproduction treatment (ART) outcomes. METHODS: DF in 360 couples (230 IVF and 130 ICSI) was measured by the alkaline Comet assay in semen and in sperm following density gradient centrifugation (DGC) and compared with fertilization rate (FR), embryo cumulative scores (ECS(1)) for the total number of embryos/treatment, embryos transferred (ECS(2)), clinical pregnancy (CP) and spontaneous pregnancy loss. MB were also measured using formamidopyrimidine DNA glycosylase to convert them into strand breaks. RESULTS: In IVF, FR and ECS decreased as DF increased in both semen and DGC sperm, and couples who failed to achieve a CP had higher DF than successful couples (+12.2% semen, P = 0.004; +9.9% DGC sperm, P = 0.010). When MB were added to existing strand breaks, total DF was markedly higher (+17.1% semen, P = 0.009 and +13.8% DGC sperm, P = 0.045). DF was not associated with FR, ECS or CP in either semen or DGC sperm following ISCI. In contrast, by including MB, there was significantly more DNA damage (+16.8% semen, P = 0.008 and +15.5% DGC sperm, P = 0.024) in the group who did not achieve CP. CONCLUSIONS: DF can predict ART outcome for IVF. Converting MB into further DNA strand breaks increased the test sensitivity, giving negative correlations between DF and CP for ICSI as well as IVF.
BACKGROUND: Many preterm infants who survive go on to develop chronic lung disease. This is probably due to persistent inflammation in the lungs. Corticosteroids have powerful anti-inflammatory effects and have been used to treat established chronic lung disease. However, it is unclear whether any beneficial effects outweigh the adverse effects of these drugs. OBJECTIVES: To determine the relative benefits and adverse effects associated with late (> 7 days) postnatal systemic corticosteroid treatment compared with control (placebo or nothing) in the preterm infant with evolving or established chronic lung disease. SEARCH METHODS: We sought randomised controlled trials (RCTs) of postnatal corticosteroid therapy from the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 8), MEDLINE (1966 through August 2013), handsearching paediatric and perinatal journals, and by examining previous review articles and information received from practising neonatologists. When possible, we contacted authors of all studies to confirm details of reported follow-up studies or to obtain any information about long-term follow-up where none had been reported. SELECTION CRITERIA: We selected RCTs of postnatal corticosteroid treatment initiated after seven days after birth in preterm infants with evolving or established chronic lung disease for this review. DATA COLLECTION AND ANALYSIS: We extracted and analysed data regarding clinical outcomes including mortality, chronic lung disease, death or chronic lung disease, failure to extubate, complications in the primary hospitalisation, and long-term health outcomes MAIN RESULTS: Twenty-one RCTs enrolling a total of 1424 participants were eligible for this review. All were randomised controlled trials, but the methods for random allocation were not always clear. Allocation concealment, blinding of the intervention and blinding of the outcome assessments were mostly satisfactory. Late steroid treatment was associated with a reduction in neonatal mortality (at 28 days), but not mortality at discharge or latest reported age. Benefits of delayed steroid treatment included reductions in failure to extubate by three, seven or 28 days, chronic lung disease at both 28 days and 36 weeks' postmenstrual age, need for late rescue treatment with dexamethasone, discharge on home oxygen, and death or chronic lung disease at both 28 days and 36 weeks' postmenstrual age. There was a trend towards an increase in risk of infection and gastrointestinal bleeding, but not necrotising enterocolitis. Short-term adverse affects included hyperglycaemia, glycosuria and hypertension. There was an increase in severe retinopathy of prematurity, but no significant increase in blindness. There was a trend towards a reduction in severe intraventricular haemorrhage, but only 247 infants were enrolled in five studies reporting this outcome. The trends to an increase in cerebral palsy or abnormal neurological examination were partly offset by a trend in the opposite direction in death before late follow-up. The combined rate of death or cerebral palsy was not significantly different between steroid and control groups. Major neurosensory disability, and the combined rate of death or major neurosensory disability, were not significantly different between steroid and control groups. There were no substantial differences between groups for other outcomes in later childhood, including respiratory health or function, blood pressure or growth, although there were fewer with a clinically important reduction in the forced expired volume in one second (FEV1) on respiratory function testing. AUTHORS' CONCLUSIONS: The benefits of late corticosteroid therapy may not outweigh actual or potential adverse effects. Although there continues to be concern about an increased incidence of adverse neurological outcomes in infants treated with postnatal steroids, this review of postnatal corticosteroid treatment for chronic lung disease initiated after seven days of age suggests that late therapy may reduce neonatal mortality without significantly increasing the risk of adverse long-term neurodevelopmental outcomes. However, the methodological quality of the studies determining the long-term outcome is limited in some cases; in some studies the surviving children have only been assessed before school age, when some important neurological outcomes cannot be determined with certainty, and no study was sufficiently powered to detect increased rates of important adverse long-term neurosensory outcomes. Given the evidence of both benefits and harms of treatment, and the limitations of the evidence at present, it appears prudent to reserve the use of late corticosteroids for infants who cannot be weaned from mechanical ventilation and to minimise the dose and duration of any course of treatment.
BACKGROUND: Keeping vulnerable preterm infants warm is problematic even when recommended routine thermal care guidelines are followed in the delivery suite. OBJECTIVES: To assess efficacy and safety of interventions designed for prevention of hypothermia in preterm and/or low birthweight infants applied within 10 minutes after birth in the delivery suite compared with routine thermal care. SEARCH STRATEGY: We used the standard search strategy of the Cochrane Neonatal Review Group (CNRG). The review was updated in October 2009. SELECTION CRITERIA: Trials using randomised or quasi-randomised allocations to test a specific intervention designed to prevent hypothermia, (apart from 'routine' thermal care) applied within 10 minutes after birth in the delivery suite to infants of < 37 weeks' gestational age or birthweight </= 2500 g. DATA COLLECTION AND ANALYSIS: We used the methods of the CNRG for data collection and analysis. MAIN RESULTS: 1) Barriers to heat loss [5 studies; plastic wrap or bag (3), plastic cap (1), stockinet cap (1)]:Plastic wraps or bags were effective in reducing heat losses in infants < 28 weeks' gestation (4 studies, n = 223; WMD 0.68 degrees C; 95% CI 0.45, 0.91), but not in infants between 28 to 31 week's gestation. Plastic caps were effective in reducing heat losses in infants < 29 weeks' gestation (1 study, n = 64; MD 0.80 degrees C; 95% CI 0.41, 1.19). There was insufficient evidence to suggest that either plastic wraps or plastic caps reduce the risk of death within hospital stay. There was no evidence of significant differences in other clinical outcomes for either the plastic wrap/bag or the plastic cap comparisons. Stockinet caps were not effective in reducing heat losses.2) External heat sources [2 studies; skin-to-skin (1), transwarmer mattress (1)]:Skin-to-skin care (SSC) was shown to be effective in reducing the risk of hypothermia when compared to conventional incubator care for infants (1 study, n = 31; RR 0.09; 95% CI 0.01, 0.64). The transwarmer mattress reduced the incidence of hypothermia on admission to NICU in VLBW infants (1 study, n = 24; RR 0.30; 95% CI 0.11, 0.83). AUTHORS' CONCLUSIONS: Plastic wraps or bags, plastic caps, SSC and transwarmer mattresses all keep preterm infants warmer leading to higher temperatures on admission to neonatal units and less hypothermia. However, the small numbers of infants and studies and the absence of long-term follow-up mean that firm recommendations for clinical practice cannot be given.
BACKGROUND: Polycystic ovary syndrome (PCOS) is characterised by infrequent or absent ovulation, and high levels of androgens and insulin (hyperinsulinaemia). Hyperinsulinaemia occurs secondary to insulin resistance and is associated with an increased biochemical risk profile for cardiovascular disease and an increased prevalence of diabetes mellitus. Insulin-sensitising agents such as metformin may be effective in treating PCOS-related anovulation. This is an update of Morley 2017 and only includes studies on metformin. OBJECTIVES: To evaluate the effectiveness and safety of metformin in combination with or in comparison to clomiphene citrate (CC), letrozole and laparoscopic ovarian drilling (LOD) in improving reproductive outcomes and associated gastrointestinal side effects for women with PCOS undergoing ovulation induction. SEARCH METHODS: We searched the following databases from inception to December 2018: Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL. We searched registers of ongoing trials and reference lists from relevant studies. SELECTION CRITERIA: We included randomised controlled trials of metformin compared with placebo, no treatment, or in combination with or compared with CC, letrozole and LOD for women with PCOS subfertility. DATA COLLECTION AND ANALYSIS: statistic and reported quality of the evidence for primary outcomes and reproductive outcomes using GRADE methodology. MAIN RESULTS: = 36%; 6 studies, 781 women; low-quality evidence) and no studies reported gastrointestinal side effects. AUTHORS' CONCLUSIONS: Our updated review suggests that metformin may be beneficial over placebo for live birth however, more women probably experience gastrointestinal side effects. We are uncertain if metformin plus CC improves live birth rates compared to CC alone, but gastrointestinal side effects are probably increased with combined therapy. When metformin was compared with CC, data for live birth were inconclusive, and the findings were limited by lack of evidence. Results differed by body mass index (BMI), emphasising the importance of stratifying results by BMI. No studies reported gastrointestinal side effects in this comparison. Due to the low quality of the evidence, we are uncertain of the effect of metformin on miscarriage in all three comparisons.
BACKGROUND: Most preterm infants who develop necrotising enterocolitis (NEC) have received enteral feeds. Uncertainty exists about which aspects of the feeding regimen affect the risk of NEC. AIM: To examine associations between various enteral feeding practices and the development of NEC in preterm infants. METHODS: Multicentre case-control study. 53 preterm infants with NEC were enrolled together with a gestational age frequency-matched control without NEC from a randomly selected neonatal unit. Clinical and feeding data were extracted and compared between the groups. RESULTS: Significantly fewer cases than controls had received human breast milk (75% vs 91%; OR 0.32, 95% CI 0.11 to 0.98). The day on which enteral feeding was started did not differ significantly (mean (SD) days after birth: cases 2.9 (2.8) and controls 2.8 (1.8)). The mean (SD) duration of trophic feeding (<1 ml/kg/h) was significantly shorter in the cases (3.3 (3.1) days) than controls (6.2 (6.7) days) (mean difference (MD) -2.9, 95% CI -4.9 to -0.9) days. Cases were fully fed significantly earlier than controls (mean (SD) days after birth: cases 9.9 (4.2) and controls 14.3 (9.8); MD -4.4, 95% CI -7.3 to -1.5). CONCLUSIONS: These data suggest that the duration of trophic feeding and rate of advancement of feed volumes may be modifiable risk factors for NEC in preterm infants. Further randomised controlled trials are warranted to assess the effect of different rates of feed advancement on the incidence of NEC, as well as other outcomes.
BACKGROUND: On the basis of evidence from non-randomised studies, it has been recommended that all babies born through thick meconium should have their tracheas intubated so that suctioning of their airways can be performed. The aim is to reduce the incidence and severity of meconium aspiration syndrome. However, for term babies who are vigorous at birth endotracheal intubation may be both difficult and unnecessary. OBJECTIVES: To determine if endotracheal intubation and suction of the airways at birth in vigorous term meconium-stained babies is more beneficial than routine resuscitation including aspiration of the oro-pharynx. SEARCH STRATEGY: The search was made from Oxford Database of Perinatal Trials, the Neonatal Trials Registry of the Cochrane Neonatal Collaborative Review Group and information obtained from knowledgeable practising neonatologists. SELECTION CRITERIA: Randomised trials which compared a policy of routine vs no (or selective) use of endotracheal intubation and aspiration in the immediate management of vigorous term meconium-stained babies at birth. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality, meconium aspiration syndrome, other respiratory conditions, pneumothorax, need for oxygen supplementation, stridor, convulsions and hypoxic-ischaemic encephalopathy were abstracted and analysed using Revman 3.1.1. MAIN RESULTS: Four randomised controlled trials of endotracheal intubation at birth in vigorous term meconium-stained babies were identified. Meta-analysis of these trials does not support routine use of endotracheal intubation at birth in vigorous meconium-stained babies to reduce mortality, meconium aspiration syndrome, other respiratory symptoms or disorders, pneumothorax, oxygen need, stridor, HIE and convulsions. REVIEWER'S CONCLUSIONS: Routine endotracheal intubation at birth in vigorous term meconium-stained babies has not been shown to be superior to routine resuscitation including oro-pharyngeal suction. This procedure cannot be recommended for vigorous infants until more research is available.
We compared the analgesic efficacy and safety of remifentanil and pethidine via patient controlled analgesia for women in established uncomplicated labour. Women received either remifentanil 40 microg with a 2-min lockout (n = 20) or pethidine 15 mg with a 10-min lockout (n = 19). Visual analogue scores for pain during the study and for overall pain were similar for both groups (mean (SD) 6.4 (1.5) cm for remifentanil and 6.9 (1.7) cm for pethidine). The area under the curve for visual analogue scores of satisfaction with analgesia was higher for remifentanil than for pethidine (p = 0.001). Maternal arterial oxygen saturation was similar in both groups. Neurologic and Adaptive Capacity Scores at 30 min were higher for remifentanil than for pethidine (median (interquartile range [range]) 36 (34.5-37 [32-39]) vs 34 (33-35 [30-35]), respectively; p = 0.003).
OBJECTIVE: Diabetes during pregnancy is a strong risk factor for obesity in the offspring, but the age at which this association becomes apparent is unknown. The purpose of this study was to examine the relation of glycemia during pregnancy with anthropometry in offspring of nondiabetic pregnant women from the Belfast U.K. center of the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. RESEARCH DESIGN AND METHODS: Women from the HAPO Study were invited to participate in follow-up of their offspring aged 2 years. Measurements included height, weight, and thickness of triceps, subscapular, and suprailiac skinfolds. RESULTS: A total of 1,165 offspring (73% of eligible children; 598 boys and 567 girls) were seen from ages 22-30 completed months. The only association that reached statistical significance was between categories of maternal 1-h glucose and BMI Z score >or=85th percentile at 2 years (P = 0.017). Overall the correlations between maternal glucose during pregnancy and BMI Z score at age 2 years were weak (fasting glucose r = 0.05, P = 0.08; 1-h glucose r = 0.04, P = 0.22; 2-h glucose r = 0.03, P = 0.36; and area under the curve for glucose r = 0.04, P = 0.18). CONCLUSIONS: This study found little association between maternal glucose during pregnancy and obesity in the offspring at this young age. These findings are not unexpected given that study results for young offspring whose mothers had diabetes during pregnancy were indistinguishable from those for normal offspring at this age. It will be interesting to see whether, as these children age, maternal glucose during pregnancy in the ranges included in the HAPO Study will be associated with obesity in their children.
BACKGROUND: Corticosteroids have been used widely after birth in preterm infants with respiratory failure; hydrocortisone may be preferable to other corticosteroids for this purpose. OBJECTIVES: To determine if postnatal hydrocortisone is useful to prevent or treat bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Randomised controlled trials (RCTs) of postnatal hydrocortisone therapy to prevent or treat BPD were sought. Data regarding clinical outcomes including mortality, BPD, death or BPD, complications during the primary hospitalisation, and long-term outcome were abstracted and analysed using RevMan 5. RESULTS: Eight RCTs enrolling a total of 880 participants were eligible. In all trials treatment was started in the first week of life; there were no trials of treatment started in infants who were chronically ventilator-dependent after the first week of life with established or evolving BPD. A meta-analysis of the available trials demonstrated little evidence for a direct effect of hydrocortisone on the rates of BPD, mortality, or the combined outcome of BPD or mortality. Hydrocortisone in the doses used in these eight studies had few beneficial or harmful effects; the notable exception was an increase in gastrointestinal perforation. CONCLUSIONS: Postnatal hydrocortisone in the doses and regimens used in the reported trials has few beneficial or harmful effects and cannot be recommended for prevention of BPD. There are no randomised trials to substantiate the use of hydrocortisone in chronically ventilator-dependent infants with established or evolving BPD.
BACKGROUND: Dexamethasone treatment started soon after birth is controversial. OBJECTIVES: To determine if postnatal dexamethasone treatment during the first week of life is beneficial in preventing bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Randomised controlled trials of postnatal dexamethasone therapy started in the first week of life in infants at risk of BPD were sought using methods of the Cochrane Collaboration. Data regarding clinical outcomes including mortality, BPD, death or BPD, complications during the primary hospitalisation, and long-term outcome were abstracted and analysed using RevMan 5. RESULTS: 20 randomised controlled trials enrolling a total of 2,860 participants were eligible for inclusion. Meta-analysis of these trials demonstrated significant benefits as regards earlier extubation and decreased risks of BPD at both 28 days' and 36 weeks' postmenstrual age (PMA), death or BPD at 28 days' and 36 weeks' PMA, patent ductus arteriosus and severe retinopathy of prematurity. Gastrointestinal bleeding and intestinal perforation were important adverse effects, and the risks of hyperglycaemia and hypertension were also increased. In the seven trials (921 infants) that reported late outcomes, cerebral palsy and the combined outcome of death or cerebral palsy were significantly more common in those treated with dexamethasone. CONCLUSIONS: The benefits of early dexamethasone treatment (≤7 days) to prevent BPD do not outweigh the known or potential adverse effects of this treatment, and it cannot be recommended for routine clinical practice.
BACKGROUND: Periconceptional folic acid prevents neural tube defects (NTDs), but it is uncertain whether there are benefits for offspring neurodevelopment arising from continued maternal folic acid supplementation beyond the first trimester. We investigated the effect of folic acid supplementation during trimesters 2 and 3 of pregnancy on cognitive performance in the child. METHODS: We followed up the children of mothers who had participated in a randomized controlled trial in 2006/2007 of Folic Acid Supplementation during the Second and Third Trimesters (FASSTT) and received 400 μg/d folic acid or placebo from the 14th gestational week until the end of pregnancy. Cognitive performance of children at 7 years was evaluated using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) and at 3 years using the Bayley's Scale of Infant and Toddler Development (BSITD-III). RESULTS: From a total of 119 potential mother-child pairs, 70 children completed the assessment at age 7 years, and 39 at age 3 years. At 7 years, the children of folic acid treated mothers scored significantly higher than the placebo group in word reasoning: mean 13.3 (95% CI 12.4-14.2) versus 11.9 (95% CI 11.0-12.8); p = 0.027; at 3 years, they scored significantly higher in cognition: 10.3 (95% CI 9.3-11.3) versus 9.5 (95% CI 8.8-10.2); p = 0.040. At both time points, greater proportions of children from folic acid treated mothers compared with placebo had cognitive scores above the median values of 10 (girls and boys) for the BSITD-III, and 24.5 (girls) and 21.5 (boys) for the WPPSI-III tests. When compared with a nationally representative sample of British children at 7 years, WPPSI-III test scores were higher in children from folic acid treated mothers for verbal IQ (p < 0.001), performance IQ (p = 0.035), general language (p = 0.002), and full scale IQ (p = 0.001), whereas comparison of the placebo group with British children showed smaller differences in scores for verbal IQ (p = 0.034) and full scale IQ (p = 0.017) and no differences for performance IQ or general language. CONCLUSIONS: Continued folic acid supplementation in pregnancy beyond the early period recommended to prevent NTD may have beneficial effects on child cognitive development. Further randomized trials in pregnancy with follow-up in childhood are warranted. TRIAL REGISTRATION: ISRCTN ISRCTN19917787 . Registered 15 May 2013.
Male infertility is a major cause of problems for many couples in conceiving a child. Recently, lifestyle pastimes such as alcohol, tobacco and marijuana have been shown to have further negative effects on male reproduction. The endocannabinoid system (ECS), mainly through the action of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) at cannabinoid (CB(1), CB(2)) and vanilloid (TRPV1) receptors, plays a crucial role in controlling functionality of sperm, with a clear impact on male reproductive potential. Here, sperm from fertile and infertile men were used to investigate content (through LC-ESI-MS), mRNA (through quantitative RT-PCR), protein (through Western Blotting and ELISA) expression, and functionality (through activity and binding assays) of the main metabolic enzymes of AEA and 2-AG (NAPE-PLD and FAAH, for AEA; DAGL and MAGL for 2-AG), as well as of their binding receptors CB(1), CB(2) and TRPV1. Our findings show a marked reduction of AEA and 2-AG content in infertile seminal plasma, paralleled by increased degradation: biosynthesis ratios of both substances in sperm from infertile versus fertile men. In addition, TRPV1 binding was detected in fertile sperm but was undetectable in infertile sperm, whereas that of CB(1) and CB(2) receptors was not statistically different in the two groups. In conclusion, this study identified unprecedented alterations of the ECS in infertile sperm, that might impact on capacitation and acrosome reaction, and hence fertilization outcomes. These alterations might also point to new biomarkers to determine male reproductive defects, and identify distinct ECS elements as novel targets for therapeutic exploitation of ECS-oriented drugs to treat male fertility problems.
BACKGROUND: Dexamethasone has powerful anti-inflammatory effects and has been used to treat established bronchopulmonary dysplasia (BPD), but it is uncertain whether the benefits outweigh the risks of treatment. OBJECTIVES: To determine the effect of late (>7 days) postnatal dexamethasone treatment compared with control (placebo or nothing) to prevent or treat BPD in the preterm infant. METHODS: Randomised controlled trials (RCTs) of late postnatal dexamethasone therapy to treat or prevent BPD were sought using methods of the Cochrane Collaboration. Data regarding clinical outcomes including mortality, BPD, death or BPD, complications during the primary hospitalisation, and long-term outcome were abstracted and analysed using RevMan 5. RESULTS: 19 RCTs enrolling 1,345 participants were eligible for this review. Late dexamethasone treatment reduced neonatal mortality, but not later mortality. Benefits of late dexamethasone included reductions in failure to extubate, BPD and the combined outcome of death or BPD. There were clear short-term complications, including hyperglycaemia and hypertension, but not intestinal perforation. Trends of an increase in cerebral palsy or abnormal neurological examination were partly offset by a trend in the opposite direction in death before late follow-up. CONCLUSIONS: The benefits of late dexamethasone may not outweigh actual or potential adverse effects. Given the evidence of both benefits and harms of treatment, and the limitations of the evidence at present, it appears prudent to reserve the use of late dexamethasone to infants who cannot be weaned from mechanical ventilation, and to minimise the dose and duration of any course of treatment.
The human fetus learns about its chemosensory environment and this influences its behavior at birth and during the nursing period. This study examined whether prenatal experience could influence behavior much later in life. The dietary preference of two groups of children (8- to 9-years old) was examined. Mothers of one group had consumed garlic during pregnancy, mothers of the control group had not. Children received two tests, 1 month apart, of a meal containing two portions of potato gratin, one flavored with garlic. The total amount of potato, and the percentage of garlic flavored potato, eaten was calculated and examined separately by ANOVA for factors of prenatal exposure, the child's sex, and trial. Children prenatally exposed to garlic ate significantly more garlic flavored potato and a significantly greater overall amount of potato on trial 2, compared to controls. The results demonstrate prenatal experience may affect behavior well into childhood.