Search

Background: Arterial pressure measurements are important to monitor vital function in neonates, and values are known to be dependent of gestational and postnatal age. Current reference ranges for mean arterial pressure in neonates have been derived from small samples and combined data of noninvasive and invasive measurements. We aimed to define reference values for noninvasive mean, systolic, and diastolic blood pressure during the first week of life in otherwise healthy preterm and term neonates defined by gestational and postnatal age. Methods: In this retrospective cohort study in a neonatal intensive care unit (NICU) in a Dutch tertiary paediatric hospital, we included the noninvasive blood pressures of neonates admitted between 2016 and 2018, with exclusion of those with severe comorbidities (major cardiac malformations, intracerebral haemorrhage, and tracheal intubation >6 h). We defined the median (P50) with −2 standard deviations (SD) (P0.23), −1 SD (P16), +1 SD (P84), and +2 SD (P97.7) for gestational age and postnatal age using quantile regression, percentiles provided online (http://bloodpressure-neonate.com/). Results: A total of 607 neonates, with 5885 measurements, fulfilled the inclusion criteria. The P50 values of mean noninvasive arterial blood pressure in extreme preterm infants steeply increased during the first day after birth and gradually increased within a week from 27 to 49 mm Hg at 24 h of gestational age, and from 49 to 61 mm Hg at 41 weeks of gestational age. Conclusions: These reference values for noninvasive blood pressure in neonates in the NICU for various gestational age groups provide guidance for clinical decision-making in healthy and diseased neonates during anaesthesia and sedation.

Objective: The aim of the study was to evaluate the oxygen saturation index (OSI) as an early predictor of clinical deterioration in infants with congenital diaphragmatic hernia (CDH). Methods: A single-center retrospective cohort study was conducted in consecutive infants with isolated CDH with continuous OSI measurements collected in the first 24 h after birth between June 2017 and July 2021. Outcomes of interest were pulmonary hypertension, extracorporeal membrane oxygenation (ECMO)-therapy, and mortality. We evaluated the discriminative values of the maximum OSI value and of mean OSI values with receiver operator characteristic (ROC) analysis and the area under the ROC curve. Results: In 42 infants with 49,473 OSI measurements, the median OSI was 5.0 (interquartile range 3.1–10.6). Twenty-seven infants developed pulmonary hypertension on a median of day 1 (1-1), of which 15 infants had an indication for ECMO-therapy, and 6 infants died. Maximum OSI values were associated with pulmonary hypertension, ECMO-therapy, and mortality. Mean OSI values had an acceptable discriminative ability for pulmonary hypertension and an excellent discriminative ability for ECMO-therapy and mortality. Although OSI measurements were not always present in the first hours after birth, we determined discriminative cut-offs for mean OSI values already in these first hours for pulmonary hypertension, the need for ECMO-therapy, and mortality. Conclusions: Continuous OSI evaluation is a promising modality to identify those infants at highest risk for clinical deterioration already in the first hours after birth. This provides an opportunity to tailor postnatal management based on the individual patient’s needs.

Background Adequate pain management for preterm born neonates suffering from the extremely painful disease necrotizing enterocolitis (NEC) is essential, since neonatal exposure to pain is related to negative short-term and long-term consequences. The aim of this study was to describe the current pain management and its effectiveness in NEC patients. Methods In this single-center, retrospective study, neonates (gestational age < 32 weeks and/or birth weight < 1500 g) with NEC Bell’s stage II or III were included. Information on pain (based on COMFORTneo and NRS scores) and analgesic therapy was collected and analyzed for the acute disease period. Results Of 79 patients included, 74 (94%) received intravenous analgesic therapy: most commonly morphine, fentanyl, and acetaminophen. The median COMFORTneo score was 11 (IQR 10–11), however, 49 patients had at least one COMFORTneo score ≥ 14 indicating pain. Nineteen patients had persistent high pain scores ≥ 14 with a median duration of 7.2 h (IQR 2.8–14.0). Conclusions This study showed that despite analgesic therapy, most NEC patients showed signs of pain, and in some, pain persisted for several hours. It suggests that current analgesic therapy frequently failed to prevent pain and existing pain was often insufficiently treated. This supports the urgent need for individualized pain management guidelines for NEC patients. Impact This study is unique in reporting on pain management in neonates suffering from necrotizing enterocolitis (NEC) during the full acute disease period. Despite analgesic therapy, the majority of NEC patients experience pain, and in some patients, pain persists for several hours. These findings highlight the need for improvement of neonatal pain management in NEC patients, including better pain monitoring and guidelines for individualized analgesic therapy. Improved pain management guidelines may help to prevent short-term and long-term consequences of neonatal exposure to pain, as well as excessive exposure to opioids.

Background: In nonpregnant populations, higher serum ferritin, which reflects high iron stores, is associated with an increased risk of hypertension. We hypothesized that a dysregulated maternal iron status in early pregnancy may lead to impaired gestational hemodynamic adaptations, leading to an increased risk of gestational hypertensive disorders. Objectives: We examined the associations of maternal iron status with maternal blood pressure, placental hemodynamic parameters, and the risks of gestational hypertensive disorders. Methods: In a population-based prospective cohort study among 5983 pregnant women, we measured maternal serum ferritin, transferrin saturation, serum iron, and transferrin concentrations at a median of 13.2 weeks gestation (95% range, 9.6-17.6). Maternal blood pressure was measured in early pregnancy, mid pregnancy, and late pregnancy, and placental hemodynamic parameters in mid pregnancy and late pregnancy were measured by ultrasound. Information on gestational hypertensive disorders was collected from medical records. We examined the associations of maternal early pregnancy iron status with maternal systolic and diastolic blood pressure, placental hemodynamic parameters, and the risks of gestational hypertensive disorders using linear and logistic regression models. Results: Higher maternal early pregnancy serum ferritin concentrations were associated with higher systolic and diastolic blood pressure throughout pregnancy in the basic models (P values < 0.05). After adjustment for maternal inflammation, sociodemographic and lifestyle factors, higher maternal early pregnancy serum ferritin concentrations were only associated with a higher early pregnancy diastolic blood pressure [0.27 (95% CI, 0.03-0.51) mmHg per SD score increase in serum ferritin] and with a higher mid pregnancy umbilical artery pulsatility index (P < 0.05). No associations with the risk of gestational hypertensive disorders were present. Conclusions: No consistent associations were present of maternal iron status in early pregnancy with gestational hemodynamic adaptations or the risks of gestational hypertensive disorders. Further studies are needed to examine the potential role of iron metabolism in the development of gestational hypertensive disorders within higher-risk populations.

Background: Internationally recognized guidelines recommend the judicious use of low oxygen (21–30%), titrated to peripheral oxygen saturation targets, for the initiation of resuscitation of very and extremely preterm infants (Aims: This study aims to assess the effect of various initial oxygen concentrations on (1) all-cause mortality, chronic lung disease, intraventricular hemorrhage, and retinopathy of prematurity; and (2) reaching the prescribed oxygen saturation targets by 5 min after birth, in preterm infants requiring resuscitation. Methods: We will conduct a systematic review and network meta-analysis using individual participant data. Studies of preterm infants Discussion: This is the first individual participant data network meta-analysis of initial oxygen concentrations for the resuscitation of preterm infants. This novel approach may address long-standing uncertainty regarding optimal oxygen supplementation practice for the resuscitation of preterm infants

The study objective was to explore associations of fetal and infant weight patterns and preterm birth with sleep and 24-h activity rhythm parameters at school-age. In our prospective population-based study, 1327 children were followed from birth to age 10–15 years. Fetal weight was estimated using ultrasound in the second and third trimester of pregnancy. Birth weight and gestational age were available from midwife registries. Infant weight was measured at 6, 12 and 24 months. Fetal and infant weight acceleration or deceleration were defined as a change of >0.67 standard deviation between the corresponding age intervals. At school-age, sleep duration, sleep efficiency, wake after sleep onset, social jetlag, inter-daily stability, and intra-daily variability were assessed using tri-axial wrist actigraphy for 9 consecutive nights. We observed that low birth weight (

ObjectiveTo determine the effects of lower (≤0.3) versus higher (≥0.6) initial fractional inspired oxygen (FiO2) for resuscitation on death and/or neurodevelopmental impairment (NDI) in infants DesignMeta-analysis of individual patient data from three randomised controlled trials.SettingNeonatal intensive care units.Patients543 children InterventionRandomisation at birth to resuscitation with lower (≤0.3) or higher (≥0.6) initial FiO2.Outcome measuresPrimary: death and/or NDI at 2 years of age.Secondary: post-hoc non-randomised observational analysis of death/NDI according to 5-minute oxygen saturation (SpO2) below or at/above 80%.ResultsBy 2 years of age, 46 of 543 (10%) children had died. Of the 497 survivors, 84 (17%) were lost to follow-up. Bayley Scale of Infant Development (third edition) assessments were conducted on 377 children. Initial FiO2 was not associated with difference in death and/or disability (difference (95% CI) −0.2%, −7% to 7%, p=0.96) or with cognitive scores 2 >80% was associated with decreased disability/death (14%, 7% to 21%) and cognitive scores >85 (10%, 3% to 18%, p=0.01). Multinomial regression analysis noted decreased death with 5-minute SpO2 ≥80% (odds (95% CI) 09.62, 0.98 to 0.96) and gestation (0.52, 0.41 to 0.65), relative to children without death or NDI.ConclusionInitial FiO2 was not associated with difference in risk of disability/death at 2 years in infants

Background: Iron deficiency during early life could affect the developing lung and immune system, and influence child's respiratory or allergy outcomes in later life. Objective: To examine the associations of maternal iron status during early pregnancy with child's lung function, asthma, inhalant allergic sensitization, and physician-diagnosed inhalant allergy at school-age. Methods: In a population-based cohort study, among 3825 mother–child pairs, ferritin, transferrin concentrations, and transferrin saturation were measured from maternal venous blood samples during early pregnancy. In children at the age of 10 years, spirometry was used to determine child's lung function, current asthma and physician-diagnosed inhalant allergy were assessed by questionnaires, and inhalant allergic sensitization was measured by skin prick tests. We used multivariable regression models to examine the associations. Results: After adjustment for gestational age at maternal iron status measurement and sociodemographic or lifestyle-related confounders, a higher maternal transferrin concentration was associated with a higher risk of physician-diagnosed inhalant allergy (odds ratio [95% confidence interval]: 1.13 [1.01 to1.26]), but not with lung function, asthma, or inhalant allergic sensitization. This association did not attenuate after further adjustment for maternal hemoglobin levels or early growth factors. We observed no consistent association of maternal ferritin concentrations or transferrin saturation with child's respiratory or allergy outcomes. Conclusion: Higher maternal transferrin concentrations during pregnancy, reflecting lower serum iron levels, were associated with an increased risk of child's physician-diagnosed inhalant allergy but not lung outcomes. Underlying mechanisms and clinical implications need to be explored.

IntroductionPulmonary hypertension is a major determinant of postnatal survival in infants with a congenital diaphragmatic hernia (CDH). The current care during the perinatal stabilisation period in these infants might contribute to the development of pulmonary hypertension after birth—in particular umbilical cord clamping before lung aeration. An ovine model of diaphragmatic hernia demonstrated that cord clamping after lung aeration, called physiological-based cord clamping (PBCC), avoided the initial high pressures in the lung vasculature while maintaining adequate blood flow, thereby avoiding vascular remodelling and aggravation of pulmonary hypertension. We aim to investigate if the implementation of PBCC in the perinatal stabilisation period of infants born with a CDH could reduce the incidence of pulmonary hypertension in the first 24 hours after birth.Methods and analysisWe will perform a multicentre, randomised controlled trial in infants with an isolated left-sided CDH, born at ≥35.0 weeks. Before birth, infants will be randomised to either PBCC or immediate cord clamping, stratified by treatment centre and severity of pulmonary hypoplasia on antenatal ultrasound. PBCC will be performed using a purpose-built resuscitation trolley. Cord clamping will be performed when the infant is considered respiratory stable, defined as a heart rate >100 bpm, preductal oxygen saturation >85%, while using a fraction of inspired oxygen of Ethics and disseminationCentral ethical approval was obtained from the Medical Ethical Committee of the Erasmus MC, Rotterdam, The Netherlands (METC 2019-0414). Local ethical approval will be obtained by submitting the protocol to the regulatory bodies and local institutional review boards.Trial registration numberNCT04373902.

Internationally recognized guidelines recommend the judicious use of low oxygen (21-30%), titrated to peripheral oxygen saturation targets, for the initiation of resuscitation of very and extremely preterm infants (32 weeks' gestation). However, despite more than 10 randomized controlled trials on this question, the ideal initial oxygen concentration for this group of vulnerable infants remains uncertain.This study aims to assess the effect of various initial oxygen concentrations on (1) all-cause mortality, chronic lung disease, intraventricular hemorrhage, and retinopathy of prematurity; and (2) reaching the prescribed oxygen saturation targets by 5 min after birth, in preterm infants requiring resuscitation.We will conduct a systematic review and network meta-analysis using individual participant data. Studies of preterm infants32 weeks' gestation, randomized to initial oxygen concentration, will be included. We will systematically search medical databases and trial registries for eligible studies (published or unpublished). Records will be screened by two independent reviewers, with conflicts resolved by the inclusion of a third reviewer. Identified initial oxygen concentrations will be grouped into the following nodes: low (≤30%), intermediate (60%), and high (≥90%) oxygen. A two-step random-effects contrast-based network meta-regression will be calculated to compare and rank different oxygen concentrations. Analyses will be intention-to-treat, with the primary outcome of all-cause mortality.This is the first individual participant data network meta-analysis of initial oxygen concentrations for the resuscitation of preterm infants. This novel approach may address long-standing uncertainty regarding optimal oxygen supplementation practice for the resuscitation of preterm infants32 weeks' gestation.

Introduction To improve counseling of parents and to guide care strategies, we studied the disease course and outcomes of necrotizing enterocolitis (NEC) up to 2 years of corrected age (CA) from a multidisciplinary perspective. Materials and Methods This was a retrospective cohort study in preterm infants (birth weight Results Of 3,456 preterm infants, 200 (6%) were diagnosed with NEC, of whom 135 developed an indication for surgery within 7 days after the diagnosis; 28/135 died before surgery, and 37/107 died after an open-and-close procedure. An enterostomy was constructed in 62 patients and an end-to-end anastomosis in 15. The postoperative course was described for 77 patients, of whom 23 developed surgical complications (12/23 incisional hernias, 9/23 anastomotic strictures), 13/77 a short bowel, and 25/77 IF. Sixty-day survival after birth for medical NEC patients was 88% (hazard ratio [HR]: 0.698; p = 0.318), and for surgically treated NEC patients was 40% (HR: 3.729; p Conclusion In this cohort, the mortality rate was high, especially in surgically treated NEC patients. The surgical complication rate is comparable to previous studies, but in surviving patients, persisting IF and severe delay in growth and neurodevelopment at 2 years CA were relatively rare.

ObjectiveTo determine the combined effect of 60 genetic variants (single nucleotide polymorphisms, SNPs), previously identified as being associated with birth weight, on fetal growth and placental haemodynamics throughout pregnancy.DesignProspective birth cohort (Generation R Study).SettingGeneral multiethnic population.Participants5374 singleton liveborn children with genome-wide association arrays and fetal growth data.MethodsLongitudinal and cross-sectional analyses of a genetic score of the total number of birth weight–increasing alleles across the 59 available SNPs and repeated fetal growth and haemodynamic measures.Main outcome measuresSD scores (SDS) of fetal weight, (femur) length, head circumference, umbilical artery pulsatility index, uterine artery mean resistance index and placental weight, in different periods of pregnancy until birth.ResultsIn longitudinal analyses, the effect of the genetic score on the fetal growth measures increased throughout pregnancy (pConclusionsOur results suggest that genetic variants related to birth weight exert their combined effect on fetal growth from second half of pregnancy onwards and have no effect on placental haemodynamics.

Introduction: The oxygenation index (OI) is a marker for respiratory disease severity and adverse neonatal outcomes. The oxygen saturation index (OSI) is an alternative that allows for continuous noninvasive monitoring, but evidence for clinical use in critically ill neonates is scarce. The aim of this study was to evaluate the OSI as compared to the OI in term neonates with a congenital diaphragmatic hernia (CDH). Methods: A single-center retrospective cohort study was conducted including all live-born infants with an isolated CDH between June 2017 and December 2020. Paired values of the OI and OSI in the first 24 h after birth were collected. The relation between OI and OSI measurements was assessed, taking into account arterial pH, body temperature, and preductal versus postductal location of oxygen saturation measurement or arterial blood sampling. The predictive values for pulmonary hypertension, need for extracorporeal membrane oxygenation therapy, and survival at discharge were evaluated. Results: Of 33 subjects included, 398 paired values of the OI (median 5.8 [3.3–17.2]) and OSI (median 7.3 [3.6–14.4]) were collected. The OI and OSI correlated strongly (r = 0.77, p < 0.001). The OSI values corresponding to the clinically relevant OI values (10, 15, 20, and 40) were 8.9, 10.9, 12.9, and 20.9, respectively. The predictive values of the OI and OSI were comparable for all adverse neonatal outcomes. No difference was found in the area under the receiver operating characteristic curves for the OI and the OSI for adverse neonatal outcomes. Conclusions: The OSI could replace the OI in clinical practice in infants with a CDH.

BACKGROUND: Children with intestinal failure (IF) receiving long-term parenteral nutrition (PN) have altered body composition (BC), but data on BC changes from start of PN onwards are lacking. OBJECTIVE: We aimed to assess growth and BC in infants after neonatal intestinal surgery necessitating PN and at risk for IF, and to explore associations with clinical parameters. DESIGN: Prospective cohort study in infants after intestinal surgery. IF was defined as PN-dependency for > 60 days. Standard deviation scores (SDS) for anthropometry were calculated until 6 months corrected age. In a subgroup, fat mass (FM) and fat-free mass (FFM) were measured with air-displacement plethysmography at 2- and 6-months corrected age. SDS for length-adjusted FM index and FFM index were calculated. Associations between cumulative amount of PN and BC parameters were analyzed with linear mixed-effect models. RESULTS: Ninety-five neonates were included (54% male, 35% born

In pregnancy, iron deficiency and iron overload increase the risk for adverse pregnancy outcomes, but the effects of maternal iron status on long-term child health are poorly understood. The aim of the study was to systematically review and analyze the literature on maternal iron status in pregnancy and long-term outcomes in the offspring after birth. We report a systematic review on maternal iron status during pregnancy in relation to child health outcomes after birth, from database inception until 21 January 2021, with methodological quality rating (Newcastle-Ottawa tool) and random-effect meta-analysis. (PROSPERO, CRD42020162202). The search identified 8139 studies, of which 44 were included, describing 12,7849 mother–child pairs. Heterogeneity amongst the studies was strong. Methodological quality was predominantly moderate to high. Iron status was measured usually late in pregnancy. The majority of studies compared categories based on maternal ferritin, however, definitions of iron deficiency differed across studies. The follow-up period was predominantly limited to infancy. Fifteen studies reported outcomes on child iron status or hemoglobin, 20 on neurodevelopmental outcomes, and the remainder on a variety of other outcomes. In half of the studies, low maternal iron status or iron deficiency was associated with adverse outcomes in children. Meta-analyses showed an association of maternal ferritin with child soluble transferrin receptor concentrations, though child ferritin, transferrin saturation, or hemoglobin values showed no consistent association. Studies on maternal iron status above normal, or iron excess, suggest deleterious effects on infant growth, cognition, and childhood Type 1 diabetes. Maternal iron status in pregnancy was not consistently associated with child iron status after birth. The very heterogeneous set of studies suggests detrimental effects of iron deficiency, and possibly also of overload, on other outcomes including child neurodevelopment. Studies are needed to determine clinically meaningful definitions of iron deficiency and overload in pregnancy.

Background: Concerns are raised about the influence of rapid growth on excessive fat mass (FM) gain in early life and later cardiometabolic health of infants born preterm. Objectives: To study the association between postnatal weight gain trajectories and body composition in infancy in infants born very preterm. Methods: In infants born +5 (interquartile range 26 +1;28 +5) and birth weight 1015 g (801;1250). The majority of infants did not make up for their initial loss of weight Z-score, but growth and later body composition were within term reference values. Weight gain during NICU stay was not associated with fat mass (absolute, %FM or FM index) in infancy. Weight gain during NICU and level II hospital stay was weakly associated with higher absolute lean mass (LM), but not after adjustment for length (LM index). Weight gain in the level-II hospital was positively associated with fat mass parameters at 2 months but not at 6 months. Strongest associations were found between weight gain at home and body composition (at both time points), especially fat mass. Conclusions: Weight gain in different timeframes after preterm birth is associated with distinct parameters of body composition in infancy, with weight gain at home being most strongly related to fat mass.

Circadian rhythm disturbance (CRD) increases the risk of disease, e.g. metabolic syndrome, cardiovascular disease, and cancer. In the present study, we investigated later life adverse health effects triggered by repeated jet lag during gestation. Pregnant mice were subjected to a regular light-dark cycle (CTRL) or to a repeated delay (DEL) or advance (ADV) jet lag protocol. Both DEL and ADV offspring showed reduced weight gain. ADV offspring had an increased circadian period, and an altered response to a jet lag was observed in both DEL and ADV offspring. Analysis of the bones of adult male ADV offspring revealed reduced cortical bone mass and strength. Strikingly, analysis of the heart identified structural abnormalities and impaired heart function. Finally, DNA methylation analysis revealed hypermethylation of miR17-92 cluster and differential methylation within circadian clock genes, which correlated with altered gene expression. We show that developmental CRD affects the circadian system and predisposes to non-communicable disease in adult life.

Objective: To determine whether hospital mortality (primary outcome) is associated with duration of bradycardia without chest compressions during delivery room (DR) resuscitation in a retrospective cohort study of randomized controlled trials (RCTs) in preterm infants assigned low versus high initial oxygen concentration. Methods: Medline and EMBASE were searched from 01/01/1990 to 12/01/2020. RCTs of low vs high initial oxygen concentration which recorded serial heart rate (HR) and oxygen saturation (SpO2) during resuscitation of infants 2 < 80% at 5 min after birth had higher odds of hospital mortality. [OR 18.6 (4.3, 79.7)]. Conclusion: In preterm infants who did not receive chest compressions in the DR, prolonged bradycardia is associated with hospital mortality.

To determine the effects of lower (≤0.3) versus higher (≥0.6) initial fractional inspired oxygen (FiOMeta-analysis of individual patient data from three randomised controlled trials.Neonatal intensive care units.543 children32 weeks' gestation.Randomisation at birth to resuscitation with lower (≤0.3) or higher (≥0.6) initial FiOPrimary: death and/or NDI at 2 years of age.Secondary: post-hoc non-randomised observational analysis of death/NDI according to 5-minute oxygen saturation (SpOBy 2 years of age, 46 of 543 (10%) children had died. Of the 497 survivors, 84 (17%) were lost to follow-up. Bayley Scale of Infant Development (third edition) assessments were conducted on 377 children. Initial FiOInitial FiO

Background: Breastfeeding is considered the most optimal mode of feeding for neonates and mothers. Human milk changes over the course of lactation in order to perfectly suit the infant’s nutritional and immunological needs. Its composition also varies throughout the day. Circadian fluctuations in some bioactive components are suggested to transfer chronobiological information from mother to child to assist the development of the biological clock. This review aims to give a complete overview of studies examining human milk components found to exhibit circadian variation in their concentration. Methods: We included studies assessing the concentration of a specific human milk component more than once in 24 h. Study characteristics, including gestational age, lactational stage, sampling strategy, analytical method, and outcome were extracted. Methodological quality was graded using a modified Newcastle-Ottawa Scale (NOS). Results: A total of 83 reports assessing the circadian variation in the concentration of 71 human milk components were included. Heterogeneity among studies was high. The methodological quality varied widely. Significant circadian variation is found in tryptophan, fats, triacylglycerol, cholesterol, iron, melatonin, cortisol, and cortisone. This may play a role in the child’s growth and development in terms of the biological clock.

Aggressive parenteral nutritional practices were implemented in clinical practice over a decade ago to prevent early growth retardation in preterm infants. We aimed to study adherence to current nutritional recommendations in a population of very preterm infants, and to evaluate growth in early life.Preterm infants (gestational age30 weeks and birth weight1500 g) were included in a prospective observational cohort study. Data on parenteral and enteral intake were collected on days 1-7, 14, 21 and 28 (d28) of life. Growth data were collected at birth, at moment of maximal weight loss (dip), and either at discharge from the neonatal intensive care unit or at d28, whichever came first. Nutritional intakes were compared to recommendations of current guidelines. The target growth rate was 15-20 g/kg/d.Fifty-nine infants (63% male) were included. Median gestational age was 27 3/7 (interquartile range 25 6/7;28 4/7), and birth weight was 920 g (720;1200). Median macronutrient intakes were within or above the targets on all study days, but energy targets were not met before day 5. Median growth rates were 9.5 and 18.1 g/kg/d, when calculated from respectively birth and dip to discharge/d28. Eight (14%) versus 46 (78%) infants met the growth targets, when evaluated from respectively birth and dip to discharge/d28.In this cohort, only energy intake up to day 5 was lower than recommended. Growth targets were achieved in the majority of the infants, but only when evaluated from dip onward, not from birth.

SummaryBackground The predisposition for obesity is suggested to originate in the prenatal period. Prenatal markers are needed to identify foetuses at risk for neonatal adiposity, as early marker of childhood obesity. Objective The aim of this study is to assess the association between foetal fractional thigh volume (TVol) and neonatal percentage fat mass from mid-gestation onward. Methods In this perinatal cohort study, singleton pregnancies with term born infants were included. Foetal TVol was measured on three-dimensional ultrasound scans (3D US) obtained at 22, 26 and 32 weeks of gestation. Neonatal body composition measurement (percentage body fat (%BF)) was planned between 42+0 and 42+6-week postmenstrual age. Cross-sectional and longitudinal linear regression analyses were performed. Results Seventy-nine mother–child pairs were included. Median (interquartile range) TVol increased from 7.6 (7.1; 8.5) cm3 at 22 weeks to 36.5 (33.8; 40.9) cm3 at 32 weeks. Median neonatal %BF was 14.3% (11.7; 17.0). TVol at 22 weeks (β = −1.58, 95% CI −2.45; −0.70, explained variance 31%) was negatively associated with %BF, but no associations were found at 26 and 32 weeks of gestation. TVol growth between 22 and 32 weeks of gestation (explained variance 18%) was also statistically significantly negatively associated with %BF. Conclusions Foetal TVol is a promising 3D US marker for prediction of neonatal adiposity from mid-gestation onward.

Purpose Evaluation of ketogenic diet (KD) therapies for seizure control during pregnancy when safety and appropriate management become considerations. Until now, no information has been available on seizure reduction and human pregnancy related outcomes in women treated with KD therapies. Method We describe two cases of pregnant women with epilepsy treated with KD therapy either as monotherapy (Case 1) or as adjunctive therapy (Case 2). Results Case 1: A 27 year old woman, gravida1, started the classic KD with medium chain triglyceride (MCT) emulsion and 75g carbohydrate-restriction, later reduced to 47g. Glucose levels were 4–6mmol/L and blood ketone levels ranged from 0.2 to 1.4mmol/L. Seizure frequency decreased and seizure-free days increased. Mild side effects included intolerance to MCT, reduced serum carnitine and vitamin levels, and mild hyperlipidemia. Fetal and neonatal growth was normal as was growth and development at 12 months. Case 2: A 36 year-old nulliparous woman was treated with a 20 gram carbohydrate-restricted Modified Atkins Diet (MAD) and lamotrigine, resulting in reduction of seizure frequency to once per month prior to pregnancy. Once pregnant, carbohydrates were increased to 30g. When seizures increased, lamotrigine dose was doubled. Urine ketones trended down during second trimester. A male was born with bilateral ear deformities of unknown significance. The child had a normal neurodevelopment at eight months. Conclusion Non-pharmacological epilepsy therapies like KD and MAD may be effective during human pregnancy. However, safety still has to be established. Further monitoring to identify potential long term side effects is warranted.

Item does not contain fulltext IMPORTANCE: Infections and necrotizing enterocolitis, major causes of mortality and morbidity in preterm infants, are reduced in infants fed their own mother's milk when compared with formula. When own mother's milk is not available, human donor milk is considered a good alternative, albeit an expensive one. However, most infants at modern neonatal intensive care units are predominantly fed with own mother's milk. The benefits of add-on donor milk over formula are not clear. OBJECTIVE: To determine whether providing donor milk instead of formula as supplemental feeding whenever own mother's milk is insufficiently available during the first 10 days of life reduces the incidence of serious infection, necrotizing enterocolitis, and mortality. DESIGN, SETTINGS, AND PARTICIPANTS: The Early Nutrition Study was a multicenter, double-blind randomized clinical trial in very low-birth-weight infants (birth weight

Summary Background & aims Albumin is one of the most important plasma proteins and plays a key role in many physiologic processes, such as preserving colloid osmotic pressure, scavenging radicals, and binding and transporting bilirubin, hormones, and drugs. However, albumin concentrations are often low in preterm infants during the first days of life. We hypothesized that early parenteral lipid and high-dose amino acid (AA) administration to very low birth weight (VLBW) infants from birth onwards increases hepatic albumin synthesis rates. Methods Inborn VLBW infants were randomized to receive from birth onwards either 2.4 g amino acids/(kg · d) (control group), 2.4 g amino acids/(kg · d) plus 2 g lipids/(kg · d) (AA + lipid group), or 3.6 g amino acids/(kg · d) plus 2 g lipids/(kg · d) (high AA + lipid group). On postnatal day 2, infants received a primed continuous infusion of [U- 13 C 6 , 15 N]leucine. Mass spectrometry was used to determine the fractional and absolute albumin synthesis rates (FSR and ASR, respectively). Results In total, 28 infants (median gestational age 27 weeks (IQR 25–28), median birth weight 810 g (IQR 679–998) were studied. The median FSR was 6.5%/d in the control group, 10.6%/d in the AA group, and 12.3%/d in the high AA + lipid group, while the median was 84 mg/(kg · d) in the control group, 138 mg/(kg · d) in the AA group, and 160 mg/(kg · d) in the high AA + lipid group. Conclusion A group of VLBW infants given parenteral nutrition containing lipids and high-dose amino acids showed a higher rate of albumin synthesis compared to infants receiving no lipids and standard amounts of amino acids during the first two days of life.

BACKGROUND AND PURPOSE: Most ultrasound markers for monitoring brain growth can only be used in either the prenatal or the postnatal period. We investigated whether corpus callosum length and corpus callosum–fastigium length could be used as markers for both prenatal and postnatal brain growth. MATERIALS AND METHODS: A 3D ultrasound study embedded in the prospective Rotterdam Periconception Cohort was performed at 22, 26 and 32 weeks' gestational age in fetuses with fetal growth restriction, congenital heart defects, and controls. Postnatally, cranial ultrasound was performed at 42 weeks' postmenstrual age. First, reliability was evaluated. Second, associations between prenatal and postnatal corpus callosum and corpus callosum–fastigium length were investigated. Third, we created reference curves and compared corpus callosum and corpus callosum–fastigium length growth trajectories of controls with growth trajectories of fetuses with fetal growth retardation and congenital heart defects. RESULTS: We included 199 fetuses; 22 with fetal growth retardation, 20 with congenital heart defects, and 157 controls. Reliability of both measurements was excellent (intraclass correlation coefficient ≥ 0.97). Corpus callosum growth trajectories were significantly decreased in fetuses with fetal growth restriction and congenital heart defects (β = −2.295; 95% CI, −3.320–1.270; P < .01; β = −1.267; 95% CI, −0.972–0.562; P < .01, respectively) compared with growth trajectories of controls. Corpus callosum–fastigium growth trajectories were decreased in fetuses with fetal growth restriction (β = −1.295; 95% CI, −2.595–0.003; P = .05). CONCLUSIONS: Corpus callosum and corpus callosum–fastigium length may serve as reliable markers for monitoring brain growth from the prenatal into the postnatal period. The clinical applicability of these markers was established by the significantly different corpus callosum and corpus callosum–fastigium growth trajectories in fetuses at risk for abnormal brain growth compared with those of controls.

Background Necrotizing enterocolitis (NEC) is a severe multifactorial disease in preterm neonates associated with high morbidity and mortality. Better insight into prognostic values of the many reported factors associated with NEC is needed to enable identification of neonates at risk for NEC. The aim was to systematically review the literature to identify independent risk factors for NEC from the literature. Methods Medline, Cochrane, Embase, Pubmed and Google Scholar were searched systematically for cohort studies reporting prognostic factors for NEC in neonates using multivariable analysis. Studies were scored with the Quality In Prognosis Studies tool (QUIPS). Results From 5154 initial hits, 14 prognostic studies were included, with various designs. Study quality was rated high in three studies, moderate or low in the 11 others. Significant prognostic factors for NEC reported in at least two studies were: low birth weight, small for gestational age, low gestational age, assisted ventilation, premature rupture of membranes, black ethnicity, sepsis, outborn, hypotension (all increased risk), surfactant therapy (conflicting results) and cesarean section (lower risk). Meta-analysis was considered not feasible. Conclusion High quality studies on prognostic factors for NEC are rare. Several prognostic factors, that are not necessarily causal, are associated with NEC. High quality prognostic research is necessary to establish the predictive values of these factors. Electronic supplementary material The online version of this article (doi:10.1186/s12887-017-0847-3) contains supplementary material, which is available to authorized users.

Organic substances that consist of both an amino group (−NH2) and an acidic carboxyl group (−COOH) are named amino acids (AA). Over 300 amino acids are known to exist in nature but only 20 amino acids serve as the building blocks of protein in humans and animals. Proteins represent an important part of all cell membranes and intracellular matrix but also enzymes, blood transport molecules and hormones are proteins. All 20 amino acids must be present in the body in appropriate amounts to allow for protein synthesis and thus normal cell function and body growth. Disturbances in the metabolism of any amino acid, as seen in inborn errors of metabolism, will inevitably lead to disease, impairment or even death when left untreated. Of the 20 amino acids, 8 are called essential amino acids, as those cannot be synthesized by the human body and must therefore be provided in sufficient amounts by the diet. AA that can be synthesized by the body in sufficient amounts are called non-essential AA. Some amino acids can be sufficiently synthesized by the body under normal conditions, but fall short under conditions where the utilization of a specific AA exceeds synthesis (e.g., sepsis) or when synthesis pathways are underdeveloped (e.g., after premature birth). These amino acids are called conditionally essential or semi-essential AA (see Table 26.1). In this chapter, various methods to study AA and protein metabolism are reviewed. This is followed by discussions on the general consequences of AA under- and overnutrition in preterm infants and differences in AA metabolism during parenteral and enteral nutrition. Lastly, parenteral and enteral AA administration is discussed. Some of the non-protein AA, such as taurine or citrulline, play important roles in cell signaling and metabolism, but this is outside the scope of this chapter.

Evidence on the clinical effectiveness of probiotics in the prevention of necrotising enterocolitis (NEC) in preterm infants is conflicting and cohort studies lacked adjustment for time trend and feeding type. This study investigated the association between the introduction of routine probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum; Infloran®) on the primary outcome ‘NEC or death’. Preterm infants (gestational age

Background: Environmental influences during pregnancy are able to affect off spring phenotype with lifelong effects. Clinical applicable markers are needed to identify foetuses at risk for neonatal adiposity. This systematic review aims to 1) review the current literature on prenatal markers of neonatal fat mass, and 2) appraise the clinical applicability of the assessed markers. Methods: A systematic literature search was conducted to identify studies meeting the following inclusion criteria: 1) original research papers in English; 2) research on dynamic and measurable prenatal markers of neonatal fat mass; 3) neonatal fat mass measurement within one month after birth, using the four-compartment model, magnetic resonance imaging, dual-energy X-ray absorptiometry or air displacement plethysmography. Two reviewers independently performed study selection, assessment of methodological (QUADAS-II) and statistical quality and appraisal of clinical applicability. Results: Of 2333 studies primarily identified by the search strategy, 16 studies were included. Four of these were both methodologically and statistically of moderate or high quality. Prenatal markers investigated were ultrasound parameters, maternal biochemical markers and maternal characteristics. Markers of predefined interest were maternal pre-pregnancy body mass index, fasting glucose and HbA1c, showing varying results. A meta-analysis was not possible due to substantial methodological heterogeneity. Clinically applicability of all markers was rated poor. Conclusions: Although associations were found, no useful marker was identified, due to lack of methodological and statistical quality, inconsistent results and poor clinical applicability. No markers were investigated in the periconceptional and embryonic period. (C) 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Background: The incidence of necrotizing enterocolitis (NEC) and possibly also of sepsis is lower in preterm infants fed their own mother’s milk (hereafter ‘mother’s milk’) compared with formula-fed infants. It is unclear whether this is caused by the protective properties of breast milk or by the absence of cow’s milk. Especially in early life, mother’s milk is often unavailable to preterm infants, while minimal enteral nutrition is initiated immediately. Objectives: To determine whether there is an association between intake of mother’s milk during the first days of life and the combined outcome of sepsis, NEC and death over a prolonged period. Methods: Retrospective study in infants with a birth weight Results: In total, 349 infants were included. Intake of mother’s milk during the first 5 days of life was associated with a lower incidence of NEC, sepsis and/or death during the first 60 days of life (hazard ratio (HR) in the category 0.01–50% intake of mother’s milk: 0.49, 95% confidence interval (CI) 0.28, 0.87; HR in the category 50.01–100% intake of mother’s milk: 0.50, 95% CI 0.31, 0.83, both compared to no mother’s milk). During days 6–10, the protective effect was only present if >50% of the total intake was mother’s milk (HR = 0.37, 95% CI 0.22, 0.65). Conclusion: The type of enteral nutrition during the first 10 days of life is associated with the risk of NEC, sepsis and/or death during the first 60 days of life.