BackgroundPreterm premature rupture of membranes (PPROM) complicates 1 % of all pregnancies and occurs in one third of all preterm deliveries. Midtrimester PPROM is often followed by spontaneous miscarriage and elective termination of ongoing pregnancies is offered in many countries. The aim of this retrospective descriptive cohort study was to investigate the natural history of midtrimester PPROM in a jurisdiction where termination of pregnancy in the absence of maternal compromise is unavailable.MethodsCases of midtrimester PPROM diagnosed between 14 and 23 + 6 weeks’ gestation during April 2007 to June 2012 were identified following a manual search of all birth registers, pregnancy loss registers, annual reports, ultrasound reports, emergency room registers and neonatal death certificates at Cork University Maternity Hospital - a large (circa 8500 births per annum) tertiary referral maternity hospital in southwest Ireland. Cases where delivery occurred within 24 h of PPROM were excluded.ResultsThe prevalence of midtrimester PPROM was 0.1 % (42 cases/44,667 births). The mean gestation at PPROM was 18 weeks. The mean gestation at delivery was 20 + 5 weeks, with an average latency period of 13 days.Ten infants were born alive (23 %; 10/42). The remainder (77 %; 32/42) died in utero or intrapartum. Nine infants were resuscitated. Two infants survived to discharge. The overall mortality rate was 95 % (40/42).Five women had clinical chorioamnionitis (12 %; 5/42) but 69 % demonstrated histological chorioamnionitis. One woman developed sepsis (2.4 %; 1/42). Other maternal complications included requirement of intravenous antibiotic treatment (38 %; 17/42), retained placenta (21 %, 9/42) and post-partum haemorrhage (12 %; 5/42).ConclusionsThis study provides useful and contemporary data on midtrimester PPROM. Whilst fetal and neonatal mortality is high, long-term survival is not impossible. The increased risk of maternal morbidity necessitates close surveillance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12884-016-0813-3) contains supplementary material, which is available to authorized users.
Introduction Treatment of paediatric heart failure is based on paradigms extensively tested in the adult population assuming similar underlying pathophysiological mechanisms. Angiotensin converting enzyme inhibitors (ACEI) like enalapril are one of the cornerstones of treatment and commonly used off-label in children. Dose recommendations have been extrapolated from adult experience, but the relationship between dose and pharmacokinetics (PK) in (young) children is insufficiently studied. Furthermore, appropriate paediatric formulations are lacking. Within the European collaborative project LENA, a novel formulation of enalapril orodispersible minitablets (ODMT), suitable for paediatric administration, will be tested in (young) children with heart failure due to either dilated cardiomyopathy or congenital heart disease in two pharmacokinetic bridging studies. Paediatric PK data of enalapril and its active metabolite enalaprilat will be obtained. In a follow-up study, the safety of enalapril ODMTs will be demonstrated in patients on long-term treatment of up to 10 months. Furthermore, additional information about pharmacodynamics (PD) and ODMT acceptability will be collected in all three studies. Methods and Analysis Phase II/III, open-label, multicentre study. Children with dilated cardiomyopathy (DCM) (n = 25; 1 month to less than 12 years) or congenital heart disease (CHD) (n = 60; 0 to less than 6 years) requiring or already on ACEI will be included. Exclusion criteria include severe heart failure precluding ACEI use, hypotension, renal impairment, hypersensitivity to ACEI. For those naïve to ACEI up-titration to an optimal dose will be performed, those already on ACEI will be switched to an expected equivalent dose of enalapril ODMT and optimised. In the first 8 weeks of treatment, a PK profile will be obtained at the first dose (ACEI naïve patients) or when an optimal dose is reached. Furthermore, population PK will be done with concentrations detected over the whole treatment period. PD and safety data will be obtained at least at 2-weeks intervals. Subsequently, an intended number of 85 patients will be followed-up up to 10 months to demonstrate long-term safety, based on the occurrence of (severe) adverse events and monitoring of vital signs and renal function. Ethics and dissemination Clinical Trial Authorisation and a favourable ethics committee opinion were obtained in all five participating countries. Results of the studies will be submitted for publication in a peer-reviewed journal. Trial registration numbers EudraCT 2015-002335-17, EudraCT 2015-002396-18, EudraCT 2015-002397-21.
ObjectiveTo characterise heart failure (HF) maintenance pharmacotherapy for children across Europe and investigate how angiotensin-converting enzyme inhibitors (ACE-I) are used in this setting.MethodsA Europe-wide web-based survey was conducted between January and May 2015 among European paediatricians dedicated to cardiology.ResultsOut of 200-eligible, 100 physicians representing 100 hospitals in 27 European countries participated. All participants reported prescribing ACE-I to treat dilated cardiomyopathy-related HF and 97% in the context of congenital heart defects; 87% for single ventricle physiology. Twenty-six per cent avoid ACE-I in newborns. Captopril was most frequently selected as first-choice for newborns (73%) and infants and toddlers (66%) and enalapril for children (56%) and adolescents (58%). Reported starting and maintenance doses varied widely. Up to 72% of participants follow formal creatinine increase limits for decision-making when up-titrating; however, heterogeneity in the cut-off points selected existed. ACE-I formulations prescribed by 47% of participants are obtained from more than a single source. Regarding symptomatic HF maintenance therapy, 25 different initial drug combinations were reported, although 79% select a regimen that includes ACE-I and diuretic (thiazide and/or loop), 61% ACE-I and aldosterone antagonist; 44% start with beta-blocker, 52% use beta-blockers as an add-on drug. Of the 89 participants that prescribe pharmacotherapy to asymptomatic patients, 40% do not use ACE-I monotherapy or ACE-I-beta-blocker two-drug only combination.ConclusionsDespite some reluctance to use them in newborns, ACE-I seem key in paediatric HF treatment strategies. Use in single ventricle patients seems frequent, in apparent contradiction with current paediatric evidence. Disparate dosage criteria and potential formulation-induced variability suggest significant differences may exist in the risk-benefit profile children are exposed to. No uniformity seems to exist in the drug regimens in use. The information collected provides relevant insight into real-life clinical practice and may facilitate research to identify the best therapeutic options for HF children.
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