Estimating baseline rates of adverse perinatal and neonatal outcomes using a facility-based surveillance approach: A prospective observational study from the WHO Global Vaccine Safety Multi-Country Collaboration on safety in pregnancy.

Background: Most perinatal and neonatal deaths occur in low- and middle-income countries (LMICs), yet, quality data on burden of adverse outcomes of pregnancy is limited in such countries.

Methods: A network of 21 maternity units, across seven countries, undertook surveillance for low birthweight, preterm birth, small for gestational age (SGA), stillbirths, congenital microcephaly, in-hospital neonatal deaths, and neonatal infections in a cohort of over 85,000 births from May 2019 - August 2020. For each outcome, site-specific rates per 1,000 livebirths (or per 1,000 total births for stillbirth) and 95% confidence intervals (CI) were calculated.

Operational lessons learned in conducting an international study on pharmacovigilance in pregnancy in resource-constrained settings: The WHO Global Vaccine safety Multi-Country collaboration project.

The WHO Global Vaccine Safety Multi-Country Collaboration study on safety in pregnancy aims to estimate the minimum detectable risk for selected perinatal and neonatal outcomes and assess the applicability of standardized case definitions for study outcomes and maternal immunization in low- and middle-income countries (LMICs). This paper documents the operational lessons learned from the study. A prospective observational study was conducted across 21 hospitals in seven countries.

WHO global vaccine safety multi-country collaboration project on safety in pregnancy: Assessing the level of diagnostic certainty using standardized case definitions for perinatal and neonatal outcomes and maternal immunization.

Standardized case definitions strengthen post-marketing safety surveillance of new vaccines by improving generated data, interpretation and comparability across surveillance systems. The Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project developed standardized case definitions for 21 key obstetric and neonatal terms following the Brighton Collaboration (BC) methodology. In this prospective cohort study, we assessed the applicability of GAIA definitions for maternal immunization exposure and for low birth weight (LBW), preterm birth, small for gestational age (SGA), stillbirth, neonatal death, neonatal infection, and congenital microcephaly.

Ethical and procedural issues for applying researcher-driven multi-national paediatric clinical trials in and outside the European Union: the challenging experience of the DEEP project.

Background: We describe our experience from a multi-national application of a European Union-funded research-driven paediatric trial (DEEP-2, EudraCT 2012-000353-31; NCT01825512). This paper aims to evaluate the impact of the local and national rules on the trial authorisation process in European and non-European countries. National/local provisions and procedures, number of Ethics Committees and Competent Authorities to be addressed, documentation required, special provisions for the paediatric population, timelines for completing the authorisation process and queries received were collected; compliance with the European provisions were evaluated.

Vaccine safety surveillance in pregnancy in low- and middle-income countries using GAIA case definitions: A feasibility assessment.

Background: Global efforts to adequately monitor safety of new vaccines for pregnant women in low and middle-income countries (LMICs) are needed. The Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) project recently published case definitions based on levels of diagnostic certainty for pregnancy- and neonatal outcomes and maternal vaccination. As a preliminary step to assessing the applicability of these definitions in LMICs, WHO selected sites and conducted a feasibility assessment to evaluate their ability to identify and classify selected outcomes (preterm birth, neonatal death, neonatal invasive bloodstream infection (NI-BSI), stillbirth) and maternal vaccination.

The ethical framework for performing research with rare inherited neurometabolic disease patients.

Unlabelled: The need for performing clinical trials to develop well-studied and appropriate medicines for inherited neurometabolic disease patients faces ethical concerns mainly raising from four aspects: the diseases are rare; include young and very young patients; the neurological impairment may compromise the capability to provide 'consent'; and the genetic nature of the disease leads to further ethical implications. This work is intended to identify the ethical provisions applicable to clinical research involving these patients and to evaluate if these cover the ethical issues. Three searches have been performed on the European regulatory/legal framework, the literature and European Union-funded projects.

Microbiological, clinical and molecular findings of non-typhoidal Salmonella bloodstream infections associated with malaria, Oriental Province, Democratic Republic of the Congo.

Background: In sub-Saharan Africa, non-typhoidal Salmonella (NTS) can cause bloodstream infections, referred to as invasive non-typhoidal Salmonella disease (iNTS disease); it can occur in outbreaks and is often preceded by malaria. Data from Central Africa is limited.

Methods: Clinical, microbiological and molecular findings of NTS recovered in a blood culture surveillance project (2009-2014) were analyzed.

Severe anaemia associated with Plasmodium falciparum infection in children: consequences for additional blood sampling for research.

Background: Plasmodium falciparum infection may cause severe anaemia, particularly in children. When planning a diagnostic study on children suspected of severe malaria in sub-Saharan Africa, it was questioned how much blood could be safely sampled; intended blood volumes (blood cultures and EDTA blood) were 6 mL (children aged <6 years) and 10 mL (6-12 years). A previous review [Bull World Health Organ.

Antibiotic prescribing in DR Congo: a knowledge, attitude and practice survey among medical doctors and students.

Objectives: Antibiotic resistance (ABR) particularly hits resource poor countries, and is fuelled by irrational antibiotic (AB) prescribing. We surveyed knowledge, attitudes and practices of AB prescribing among medical students and doctors in Kisangani, DR Congo.

Methods: Self-administered questionnaires.

Short-term use of parenteral nutrition with a lipid emulsion containing a mixture of soybean oil, olive oil, medium-chain triglycerides, and fish oil: a randomized double-blind study in preterm infants.

Background: For premature neonates needing parenteral nutrition (PN), a balanced lipid supply is crucial. The authors hypothesized that a lipid emulsion containing medium-chain triglycerides (MCTs) and soybean, olive, and fish oils would be as safe and well tolerated as a soybean emulsion while beneficially influencing the fatty acid profile.

Methods: Double-blind, controlled study in 53 neonates (<34 weeks' gestation) randomized to receive at least 7 days of PN containing either an emulsion of MCTs and soybean, olive, and fish oils or a soybean oil emulsion.

Trends in preterm births in Flanders, Belgium, from 1991 to 2002.

Changes in the preterm birth rate have been attributed predominantly to increases in multiple pregnancies, associated with advanced maternal age and assisted reproduction, and to obstetric intervention. We examined their contribution to the frequencies of preterm (<37 weeks), very preterm (<32 weeks) and severely preterm (<28 weeks) birth among 700 383 singleton and twin births in Flanders from 1991 to 2002. We examined changes across four 3-year periods (triennia) with confidence interval [CI] analysis and yearly incremental rates using linear and logistic regression analyses.

The effect of changes in tPCO2 on the fractional tissue oxygen extraction--as measured by near-infrared spectroscopy--in neonates during the first days of life.

The cerebral fractional oxygen extraction (FOE) reflects the balance between cerebral oxygen delivery (OD) and consumption (VO(2)). PCO(2) affects the cerebral blood flow (CBF): hypocapnia decreases CBF and OD and increases FOE. We recently showed that the fractional tissue oxygen extraction (FTOE) reflects FOE and hypothesized that a decrease in tPCO(2) increases FTOE.

Use of the liver tissue oxygenation index as a noninvasive parameter of intestinal ischemia in rabbits.

Objective: The tissue oxygenation index (TOI), measured by spatially resolved spectroscopy (SRS), reflects the ratio between oxygenated and deoxygenated tissue hemoglobin. We investigated whether liver TOI is a noninvasive parameter for early detection of intestinal ischemia.

Methods: In seven adult New Zealand rabbits the superior mesenteric artery (SMA) and vein were exposed by laparotomy.

Cardiorespiratory events recorded on home monitors: the effect of prematurity on later serious events.

Objective: To describe severe alarms on home-documented monitoring in infants born prematurely.

Methods: In infants born at a post-menstrual age (PMA) less than 35 weeks, a polysomnography was performed before discharge. A heart rate less than 50 beats per minute (bpm) for more than 3 seconds or an apnea lasting for more than 15 seconds with a heart rate less than 60 bpm were defined as abnormal.

Use of tissue oxygenation index and fractional tissue oxygen extraction as non-invasive parameters for cerebral oxygenation. A validation study in piglets.

Objective: To evaluate the relation between cerebral tissue oxygenation index (TOI), measured with spatially resolved spectroscopy (SRS), and the different oxygenation parameters. To evaluate the relation between a new parameter named fractional tissue oxygen extraction (FTOE) and the cerebral fractional oxygen extraction (FOE).

Methods: Six newborn piglets were measured at 33, 35, and 37 degrees C and in hypocapnia.

Maturational changes in the in vivo activity of CYP3A4 in the first months of life.

Objective: To document maturational changes of the in vivo activity of CYP3A4 in the first months of life.

Methods: The contribution of tramadol (M), O-demethyl tramadol (M1, CYP2D6-mediated) and N-demethyl tramadol (M2, CYP3A4-mediated) to the overall elimination of tramadol and the log M/M2 was assessed in 24-hour urine collections during continuous intravenous tramadol administration. Correlations with perinatal characteristics (postnatal age (PNA) and postmenstrual age (PMA)) were studied.

Cryotherapy versus laser photocoagulation for threshold retinopathy of prematurity: impact on early postoperative clinical recovery.

In a retrospective study in preterms treated with either cryotherapy (n= 16, 2000-2001) or laser photocoagulation (n= 19, 2002-2005) for threshold retinopathy, a significant decrease in duration of postoperative ventilation, in postoperative administration of analgesics and in time until regain of full enteral feeding was documented in infants who received laser photocoagulation. We therefore conclude that - compared to cryotherapy - laser treatment for threshold retinopathy is associated with a faster clinical postoperative recovery.

Two female siblings with congenital heart disease, postaxial polydactyly, ectopic neuropituitary gland, hair anomalies and characteristic facial features: a new syndrome?

We present two siblings from unrelated parents presenting with intrauterine growth retardation, a congenital heart defect, postaxial polydactyly, a brain malformation (ectopic neuropituitary gland associated with a hypoplastic adenopituitary in one of them, and a hypoplastic cerebellum and vermis in the other), abnormal hair with temporal balding, a striking facial dysmorphism and, at least in the child who survived, postnatal growth retardation and severe developmental delay. This probably represents a novel syndrome.

Dopamine is not an independent risk factor for reduced amikacin clearance in extremely low-birth-weight infants.

Introduction: Important inter-individual variability in amikacin clearance was observed in preterm infants, only in part explained by gestational age (GA), birth weight, or coadministration of nonselective cyclo-oxygenase (COX) inhibitor. We therefore evaluated whether dopamine had an additional effect on amikacin clearance.

Methods: Clinical characteristics (GA, weight, COX inhibitor, dopamine, prenatal betamethasone) and amikacin pharmacokinetics were retrospectively collected in a cohort of preterm infants (GA of <31 wks, early neonatal life on respiratory support, between January 1, 1999 and January 6, 2005).

Clinical pharmacology of non opioid analgesics in neonates.

An integrated approach of neonatal analgesia starts with the systematic evaluation of pain and should be followed by effective interventions, mainly based on the appropriate (i.e. safe and effective) administration of analgesics.

O-demethylation of tramadol in the first months of life.

Objective: Assess in vivo O-demethylation activity in the first months of life.

Methods: Time-concentration profiles of tramadol (M) and O-demethyl tramadol (M1) in plasma and urine were simultaneously collected in the first 24 h of continuous intravenous tramadol administration in neonates and young infants. M and M1 were determined by high performance liquid chromatography.

Intra- and interindividual variability of glucuronidation of paracetamol during repeated administration of propacetamol in neonates.

Background: Major changes in drug clearance and metabolism are observed during infancy, in part based on ontogenic regulation of various metabolic pathways. Since paracetamol provides a good substrate to study UGT (1A6) activity, urinary metabolites of propacetamol were determined in neonates in whom propacetamol was repeatedly administered.

Methods: Paracetamol glucuronide (APAP-G), paracetamol sulphate (APAP-S) and free paracetamol were determined in urine samples of neonates during repeated administration of propacetamol.