Fecal amine metabolite analysis before onset of severe necrotizing enterocolitis in preterm infants: a prospective case-control study.

Infants developing necrotizing enterocolitis (NEC) have a different metabolomic profile compared to controls. The potential of specific metabolomics, i.e. amino acids and amino alcohols (AAA), as early diagnostic biomarkers for NEC is largely unexplored. In this multicenter prospective case-control study, longitudinally collected fecal samples from preterm infants (born <30 weeks of gestation) from 1-3 days before diagnosis of severe NEC (Bell's stage IIIA/IIIB), were analyzed by targeted high-performance liquid chromatography (HPLC). Control samples were collected from gestational and postnatal age-matched infants. Thirty-one NEC cases (15 NEC IIIA;16 NEC IIIB) with 1:1 matched controls were included. Preclinical samples of infants with NEC were characterized by five increased essential amino acids-isoleucine, leucine, methionine, phenylalanine and valine. Lysine and ethanolamine ratios were lower prior to NEC, compared to control samples. A multivariate model was rendered based on isoleucine, lysine, ethanolamine, tryptophan and ornithine, modestly discriminating cases from controls (AUC 0.67; p < 0.001). Targeted HPLC pointed to several specific AAA alterations in samples collected 1-3 days before NEC onset, compared to controls. Whether this reflects metabolic alterations and has a role in early biomarker development for NEC, has yet to be elucidated.

Is quantitative ultrasound a measure for metabolic bone disease in preterm-born infants? A prospective subcohort study.

In this study, we aimed to (a) evaluate postnatal changes in bone development in relation to growth and (b) to determine factors associated with bone development, from birth to 24 months of corrected age. The metacarpal speed of sound (mcSOS) and metacarpal bone transmission time (mcBTT) were used to evaluate bone development in 98 preterm infants, during hospitalization and follow-up. The mcSOS and mcBTT values not only declined in the first 6 weeks of hospitalization but also during follow-up. The mcSOS reached its lowest point at 12 months (ß=-34.64), while the mcBTT reached a plateau between 12 and 24 months (ß=0.06). Univariable analysis showed that gender (p=0.28), time (p<0.001), and growth parameters (p<0.001) were significant negative associated factors with mcSOS, whereas with mcBTT, time (p=0.009), length (p=0.063), length standard deviation scores (SDS) (p=0.027), head circumference (p=0.005), and head circumference SDS (p=0.007) were significant positive. The multivariable model revealed that time (ß= -3.364, p=<0.001), weight (ß=-0.007, p<0.001) and length (ß=1.163, p<0.001) for mcSOS and length (ß=-0.021, p<0.001), and length SDS (ß= 0.066, p<0.001) and head circumference (ß=0.049, p<0.001) for mcBTT remained highly significant associated factors.Conclusion: The most important finding is that mcSOS decreased and the mcBTT reached a plateau to 24 months. In both mcSOS and mcBTT, the growth parameters were significant factors.Clinical Trial Registration: N/A What is known: • Metabolic bone disease is one of the possible long term adverse outcomes after preterm birth. • Metacarpal speed of sound (mcSOS) and metacarpal bone transmission time (mcBTT) decline in the early postnatal period. What is new: • During follow-up, mcSOS further decreased and reached its lowest point at 12 months, while the mcBTT reached a plateau up to 24 months. • Postnatal nutrition in relation to comorbidity does not meet the optimal mineralization rate of the developing preterm bone.

Additional value of advanced neurosonography and magnetic resonance imaging in fetuses at risk for brain damage.

OBJECTIVE: To assess the additional value of fetal multiplanar (axial, coronal and sagittal) neurosonography and magnetic resonance imaging (MRI) to that of the standard axial ultrasound planes in diagnosing brain damage in fetuses at high risk. METHODS: This was a prospective, multicenter, observational study. Women were eligible for participation if their fetus was at risk for acquired brain anomalies. Risk factors were congenital infection, alloimmune thrombocytopenia, fetal growth restriction, trauma during pregnancy, fetal hydrops, monochorionic twins and prior ultrasound finding suggestive of an acquired brain anomaly. Examinations of the fetal brain before birth comprised axial ultrasound and advanced neurosonography biweekly and MRI once. After birth, neonatal cranial ultrasound was performed at < 24 h and at term-equivalent age. Neonatal brain MRI was performed once at term-equivalent age. An expert panel blinded to medical information, including imaging findings by the other methods, evaluated the presence of periventricular echogenicity (PVE) changes, peri- and intraventricular hemorrhage (IVH) and changes in basal ganglia and/or thalami echogenicity (BGTE) on ultrasound, and the equivalent signal intensity (SI) changes on MRI. Conclusions on imaging findings were generated by consensus. The children were followed up with examinations for psychomotor development at 1 year of age, using the Touwen examination and Alberta Infant Motor Scale, and at 2 years of age using Bayley Scale of Infant Development-III (BSID-III) and behavioral, sensory profile and linguistic questionnaires; scores > 1 SD below the mean were considered suspicious for neurodevelopmental sequelae. RESULTS: Fifty-six fetuses were examined, and in 39/56 fetuses, all fetal-imaging modalities were available. PVE/SI changes were observed in 6/39, 21/39 and 2/39 fetuses on axial ultrasound planes, multiplanar neurosonography and MRI, respectively. IVH was found in 3/39, 11/39 and 1/39 fetuses, and BGTE/SI changes in 0/39, 12/39 and 0/39 fetuses, respectively. Outcome was suspicious for neurodevelopmental sequelae in 13/46 infants at 1 year, and at 2 years, 41/41 children had scores within 1 SD of the mean on BSID-III and 20 had scores > 1 SD below the mean on the behavioral (5/38), sensory profile (17/37) and/or linguistic (6/39) questionnaires. CONCLUSIONS: In this cohort of fetuses at risk for brain damage, the severity of acquired brain anomalies was limited. Nevertheless, multiplanar neurosonography detected more fetal PVE changes, IVH and/or BGTE changes compared to the standard axial ultrasound planes and MRI. Fetal MRI did not demonstrate any anomalies that were not seen on neurosonography. Neurodevelopmental outcome at 2 years of age showed no or mild impairment in most cases. © 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Neurodevelopmental outcome at 2 years of age in preterm infants with late-onset sepsis.

Late-onset sepsis is associated with impaired neurodevelopmental outcome in preterm infants. This prospective cohort study aims to establish the effect of sepsis after 72 h of life on cognitive, psychomotor, and language development of preterm infants (below 32 weeks gestational age and/or below 1500 g). At 2 years corrected age, neurodevelopmental outcome was tested using Bayley's Scales of Infant Development-II, Lexilijst (lexical development questionnaire), and behavior checklists. Of 117 patients included, 85 experienced blood culture-proven infection. Coagulase-negative staphylococci were responsible for 55% of the episodes. No significant differences were found in cognitive, motor, and behavioral scores or lexiquotient comparing patients with versus no proven infection. When comparing three groups (coagulase-negative staphylococci, other, and negative blood culture), a significant difference was found in composite cognitive scores (p = 0.016), in favor of the coagulase-negative staphylococci group versus other causal agent group (p = 0.007). No significant differences were found in other subscales.Conclusion: In this cohort, no differences were found in neurodevelopmental outcome at 2 years corrected age between proven and no proven infection groups; confirmation in larger cohorts with a control group is needed. Patients encountering coagulase-negative staphylococci sepsis showed a significant better cognitive outcome compared to other causal agents. What is Known: • Late-onset sepsis is associated with impaired neurodevelopmental outcome in preterm infants. What is New: • Preterm infants encountering late-onset sepsis by coagulase-negative staphylococci show a better cognitive outcome in comparison to other causal infectious agents in this cohort. • No differences were found in neurodevelopment at 2 years of age in preterm infants with suspected lateonset sepsis, between proven and no proven infection groups. Confirmation is needed in larger cohorts with a substantial control group.

Placental Histology After Minor Trauma in Pregnancy: A Pilot Study.

OBJECTIVE: Trauma in pregnancy may cause placental abruption. Consequences of moderate placental injury on neurodevelopment are unknown. The aim was to evaluate placental histology after maternal trauma. METHODS: A prospective study was conducted at 2 tertiary medical centers in the Netherlands. Placentas from women exposed to maternal trauma ≥ 20 weeks' gestational age were histologically examined. Neurological follow-up of the infants was performed at 1 year of age by means of Alberta Infant Motor Scale. Histological findings were compared to placentas from pregnancies without trauma. PRINCIPAL RESULTS: Thirteen placentas were investigated in the trauma group. The control group consisted of 15 placentas. Placental pathology was seen more often in the trauma cases (11 of the 13) than in the controls (6 of the 15), P = .024. Neurological follow-up was normal. CONCLUSIONS: In this small population, majority of the placentas showed pathology after minor trauma in pregnancy without consequences for neurodevelopment at 1 year.

Neurobehavioural outcome in 6-18 year old children after trauma in pregnancy: Case-control study.

BACKGROUND: Maternal trauma complicates pregnancy in approximately 7%. Long-term development of children exposed to maternal trauma is unknown. AIM: To determine neurobehavioural outcome of children (6-18 years) born after maternal trauma in pregnancy compared to a matched control group. STUDY DESIGN: Case-control study performed at a tertiary medical centre. SUBJECTS: All consecutive children born after maternal hospitalization for trauma during pregnancy between 1995 and 2005. Controls were children born at the same hospital and period after an uneventful pregnancy. OUTCOME MEASURES: Trauma type and severity (Injury Severity Score, ≥9: severe); information from medical files at admission (cases). All mothers filled out two questionnaires about the infant; 1. concerning health, motor development and educational level, 2. concerning behavioural development through the validated Dutch version of the Child Behavior Checklist (CBCL). RESULTS: Questionnaires were returned by 34 cases and 28 controls. The traumas concerned mainly motor vehicle accidents and falls, and 3/34 had severe injuries. No differences in health, motor development, educational level and CBCL was found between the cases and controls, except for more hospitalization in the cases (p = 0.009). CONCLUSION: Long-term follow-up of a limited population of children 6-18 years after exposure of mainly non-severe trauma before birth is similar to a control population except for unexplained more hospitalization in the cases.

Trauma in pregnancy, obstetrical outcome in a tertiary centre in the Netherlands.

PURPOSE: To determine obstetrical outcome and predictive value of obstetrical symptoms and diagnostic examinations on adverse outcome after maternal trauma in pregnancy. MATERIALS AND METHODS: Retrospective study in a Dutch tertiary medical center, including women admitted for trauma in pregnancy between 1995 and 2005 and infants born from these pregnancies. Characteristics at trauma (type of trauma, severity) and obstetrical outcome were recorded, as well as prevalence and severity of trauma; prevalence of obstetrical symptoms and abnormal diagnostic examinations. Composite adverse obstetrical outcome was defined as fetal death, placental abruption, birth <37 weeks and/or birth weight <10th percentile. The predictive value of obstetrical symptoms or abnormal diagnostic tests on an adverse pregnancy outcome was analyzed (logistic regression analysis). RESULTS: Trauma admissions occurred in 10 per 1000 deliveries. Injuries were non-severe in 147/159 (92%). Obstetrical symptoms and/or abnormal diagnostic tests were present in 64/159 (40%) and 12/159 (8%) respectively. Adverse pregnancy outcome was encountered in 17/80 cases, mainly preterm births (13/80 (16%)). Severe injuries were predictive for an adverse pregnancy outcome. CONCLUSIONS: We found a considerable rate of trauma during pregnancy. There was an increased risk for preterm birth and severity of injuries was predictive for adverse outcome.

Cerebral ultrasound abnormalities in preterm infants caused by late-onset sepsis.

INTRODUCTION: This study describes cerebral ultrasound abnormalities caused by late-onset sepsis (LOS) in very preterm infants with a gestational age of < 32 weeks and/or birthweight < 1500 grams. METHODS: The prospective study ("INFANT study") included 117 preterm infants with suspected LOS. Proven LOS was defined as a positive blood culture after 72 hours of life. In case of coagulase-negative staphylococci an elevated C-reactive protein was additionally required to establish proven LOS. Patients were identified as proven LOS and patients with only clinical symptoms of LOS. Cerebral ultrasound images were obtained in the first week after birth, during/after LOS and before discharge. Cerebral findings were divided in no/minor and major abnormalities. RESULTS: Eighty-six preterm infants had proven LOS and 31 preterm infants had only clinical signs of LOS. Four infants were excluded because pre-existing major brain abnormalities. No significant differences (p = 0.624) for incidence of major brain abnormalities on cerebral ultrasound were found. CONCLUSION: No differences were revealed in prevalence of major brain abnormalities between the groups with proven LOS and with clinical signs of LOS. Both infants with a gram negative sepsis developed major brain abnormalities, whereas only two of 66 preterm infants coagulase-negative staphylococci sepsis developed major brain abnormalities.

Comparison of psychomotor outcome in patients with perinatal asphyxia with versus without therapeutic hypothermia at 4 years using the Ages and Stages Questionnaire screening tool.

INTRODUCTION: Therapeutic hypothermia improves outcome after perinatal asphyxia. The Ages and Stages Questionnaire is a screening tool to detect neurodevelopmental delay. In this study we examined the outcome of patients with perinatal asphyxia (defined as Apgar score <5 at 10 min, or continued need for resuscitation, or pH < 7.00 in umbilical cord or within one hour after birth) with and without therapeutic hypothermia treatment at the age of four years. METHODS: Cohort study of patients with perinatal asphyxia admitted to the Neonatal Intensive Care Units of the VU University Medical Center, Amsterdam and the Wilhelmina Children's Hospital, Utrecht in the year 2008. Parents were asked to fill out the 48 months Ages and Stages Questionnaire (ASQ). In Wilhelmina Children's Hospital treatment with therapeutic hypothermia was implemented in 2008, in the VU University Medical Center in 2009, providing a historical cohort. RESULTS/DISCUSSION: Twenty-three questionnaires were evaluated. Response rate of questionnaires for the VU Medical Center was 63% (n = 10) and Wilhelmina's Childrens Hospital 93% (n = 13). No significant differences were found in the mean scores between both groups. However, the untreated group scored more frequently under the -2 SD threshold. In the fine motor skills domain the difference was statistically significant (p = 0.031). In the treated group no patients developed cerebral palsy and in the untreated group two patients developed cerebral palsy. CONCLUSION: In this study patients treated with hypothermia tend to have a better neurodevelopmental outcome. No significant differences were found between the two groups, apart from the fine motor skills.

Lean mass and fat mass accretion between term age and 6 months post-term in growth-restricted preterm infants.

Early growth restriction followed by nutritional intakes that permit accelerated growth may result in adiposity and metabolic disease in later life. This study compared growth, body composition and nutritional intake between term age and 6 months post-term in 83 appropriate-for-gestational-age preterm infants with growth restriction at term age (AGA GR+), 15 AGA without growth restriction at term age (AGA GR-) and 33 small-for-gestational-age (SGA) preterm infants. AGA GR+ and SGA preterm infants had higher protein intake, higher energy intake and higher gain in weight SDS between term age and 6 months post-term, with similar lean mass (LM) and lower fat mass (FM) at 6 months post-term compared with AGA GR- preterm infants. In conclusion, despite higher energy and protein intake compared with AGA GR- preterm infants during the first 6 months post-term, AGA GR+ and SGA preterm infants restore their LM without excessive FM.

Apparent Life-Threatening Event following Maternal Use of Temazepam during Labour.

Benzodiazepines are one of the most frequently prescribed psychotropic drugs during pregnancy. Despite the fact that these drugs have been in use for a long time, there is still debate about the safety for the developing fetus and neonate. We present a case of a newborn with an apparent life-threatening event shortly after birth following maternal temazepam use during labour and advise to be reserved in prescribing any dose of any kind of benzodiazepine during labour.

Doxapram use for apnoea of prematurity in neonatal intensive care.

Apnoea of prematurity is treated with noninvasive respiratory therapy and methylxanthines. For therapy unresponsive apnoea doxapram is often prescibed in preterm neonates. The duration, dosage and route of administration of doxapram together with its efficacy was evaluated in two Dutch neonatal intensive care. Outcome concerning short-term safety and neonatal morbidity were evaluated. During 5 years, 122 of 1,501 admitted newborns <32 weeks of gestational age received doxapram. 64.8% of patients did not need intubation after doxapram. 25% of treated neonates were <27 weeks of gestation. A positive response to doxapram therapy on apnoea was associated with longer duration of doxapram usage (P < 0.001), lower mean doses (P < 0.003), and less days of intensive care (median 33 versus 42 days; P < 0.002). No patients died during doxapram therapy. Incidence of necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, persistent ductus arteriosus, or worsening of pulmonary condition did not increase during doxapram therapy. Doxapram is frequently used for apnoea of prematurity, despite a lack of data on short-term efficacy and long-term safety. Until efficacy and safety are confirmed in prospective trials, doxapram should be used with caution.

Clinical evaluation of propofol as sedative for endotracheal intubation in neonates.

AIM: To determine the effects of propofol for endotracheal intubation in neonates in daily clinical practice. METHODS: We prospectively studied the pharmacodynamic effects of intravenous propofol administration in neonates who needed endotracheal intubation at the neonatal intensive care unit. RESULTS: Propofol was used for 62 intubations in neonates with postmenstrual ages ranging from 24 + 3 weeks to 44 + 5 weeks and bodyweights ranging from 520 to 4380 g. A 2 mg/kg bodyweight propofol starting dose was sufficient in 37% of patients; additional propofol was needed less often on the first postnatal day. The mean amount of propofol used was 3.3 (±1.2) mg/kg. The success rate of intubation depended on the experience of the physician and was related to the total administered amount of propofol. Hypotension occurred in 39% of patients and occurred more often at the first postnatal day. In 15% of procedures, propofol mono therapy was insufficient. CONCLUSION: This study shows that high doses of propofol are needed to reach effective sedation in neonates for intubation, with hypotension as a side effect in a considerable percentage of patients. Further research in newborn patients needs to identify optimal propofol doses and risk factors for hypotension.

Maternal use of SSRIs, SNRIs and NaSSAs: practical recommendations during pregnancy and lactation.

Selective serotonin reuptake inhibitors (SSRIs) are increasingly used during pregnancy and lactation, with 1.8-2.8% exposed pregnancies. Given the risks of untreated maternal depression for both mother and child, adequate treatment is essential. If pharmacological treatment with SSRIs is indicated, the fetal and neonatal effects of SSRIs have to be considered, as SSRIs cross the placenta and are excreted into breast milk. The overall risk of major congenital malformations during SSRI exposure in the first trimester does not appear to be greatly increased. Depending on the variability in pharmacokinetic properties between the different SSRIs and the individual drug metabolism of mother and child, SSRI exposure during late pregnancy can lead to serotonin reuptake inhibitor-related symptoms in up to 30% of exposed infants postnatally. Symptoms are generally mild and self-limited, but need observation during at least 48 h as some infants develop severe symptoms needing intervention. Limited data are available about the long-term neurodevelopmental outcomes after SSRI exposure during pregnancy and lactation, but currently, cognitive development seems normal, while behavioural abnormalities may be increased. In this article, the available clinical data are reviewed. Additionally, the authors provide a multidisciplinary guideline for the monitoring and management of neonates exposed to SSRIs during pregnancy and lactation.

Urine gonadotropin and testosterone levels in male very-low-birthweight infants.

BACKGROUND/AIMS: The postnatal activation of the hypothalamic-pituitary-gonadal axis is more exaggerated in preterm than in full-term-born infants, and may be important for reproductive function. Our objective was to investigate this activation of the hypothalamic-pituitary-gonadal axis in male very-low-birthweight (VLBW) infants. METHODS: Twenty-one VLBW boys (gestational age 26.0-30.0 weeks), participating in the NIRTURE trial, were included. Gonadotropin and testosterone levels were measured in serial urine samples collected at 1 and 4 weeks' postnatal age, at 32 weeks' postmenstrual age, at expected date of delivery and at the corrected age of 3 and 6 months. RESULTS: Longitudinal analysis shows that after birth LH and FSH levels peak at a mean postnatal age of 1-4 weeks (mean postmenstrual age of 30-32 weeks) and decrease until 38 weeks' postnatal age (corrected age of 6 months). Testosterone levels decrease with increasing age, and this decrease is faster in infants receiving early insulin therapy. CONCLUSIONS: Serial urine sampling for measurement of gonadotropin and testosterone levels provides accurate information about the postnatal activation of the hypothalamic-pituitary-gonadal axis in VLBW boys. FSH and LH levels peak at 1-4 weeks of age. Insulin treatment causes faster decrease in testosterone levels.

Insulin resistance and the metabolic syndrome in obese children referred to an obesity center.

OBJECTIVE: The aim of this study was to describe insulin resistance and the metabolic syndrome in obese children and adolescents. SUBJECTS: The cohort consisted of 518 patients, 250 boys, 268 girls, age +/- sd: 11.8 +/- 3.2 years, BMIsds +/- sd: 2.94 +/- 0.5. A standard OGTT was performed. RESULTS: Impaired glucose tolerance was found in 9.4% of the boys and 5.5% of the girls. Impaired fasting glucose was found in 12.4% of the boys and 11.6% of the girls. The metabolic syndrome was present in 13.9% of children of 10 years or older. The proportion in which the metabolic syndrome was diagnosed was essentially not altered when pubertal groups were used instead of age groups. CONCLUSION: Both impaired fasting glucose and impaired glucose tolerance as well as the metabolic syndrome are highly prevalent among obese children and adolescents.

Relation of maternal hypertension with infant growth in a prospective birth cohort: the ABCD study.

The aim of this study was to investigate the assumed positive association of pre-existent and pregnancy-induced hypertension with the offspring's weight and length gain in the first 14 months of life. We studied 3994 pregnant women and their offspring in a prospective community-based cohort study, starting between 2003 and 2004 (Amsterdam Born Children and their Development, ABCD study). Questionnaires obtaining information about hypertension during pregnancy were completed, and this was complemented with additional information from the obstetric caregiver. Anthropometry of the offspring was followed during the first 14 months of life. Main outcome measures were presence or absence of growth acceleration in weight or length (normal: ΔSDS ⩽ 0.67 v. growth acceleration: ΔSDS > 0.67). The relation between hypertension during pregnancy and weight and length gain was addressed by logistic regression analyses. We found that pre-existent hypertension was related to growth acceleration in weight and length. After correction for birth weight and pregnancy duration, the effect remained significant for growth acceleration in weight (OR 1.89; 95% CI 1.21-2.97; P < 0.01). Pregnancy-induced hypertension showed similar results, although correction for birth weight and pregnancy duration rendered the associations non-significant. In conclusion, infants of women with pre-existent hypertension during pregnancy more frequently have growth acceleration in weight and length, and yet the mechanisms acting on postnatal growth appear to be different.

Information processing, attention and visual-motor function of adolescents born after in vitro fertilization compared with spontaneous conception.

BACKGROUND: Adverse conditions during prenatal life are associated with changes in physical and mental functioning in later life, as shown in children born preterm or small for gestational age. While recently in IVF children cardiometabolic differences have been demonstrated, there might also be risks for disturbance in cognitive functions. Therefore, this study examined information processing, attention and visual-motor function in pubertal IVF children compared with spontaneously conceived controls from subfertile parents. Results of these cognitive functions were then related to cardiometabolic measures to explore whether both can be explained by changes in fetal programming due to IVF. METHODS: A total of 139 IVF and 143 control adolescents underwent various neuropsychological tests to measure information processing, attention and visual-motor function. The results were then related to data on blood pressure and glucose levels previously obtained from the same groups. RESULTS: No differences between IVF and control adolescents were found in the various test results for information processing and attention. A slight difference was found between the groups for motor speed, but these scores were within the normal range for the test. No direct relation was found between cognitive measures and cardiometabolic outcome. CONCLUSIONS: Comparison of IVF adolescents and controls revealed no disturbances in information processing, attention and visual-motor function. In addition, these cognitive functions were not directly related to cardiometabolic outcome. Therefore, these results do not support the hypothesis that cognition is influenced by IVF conception or an altered programming of metabolic systems due to IVF, and indicate that cognitive abilities in IVF children, as measured by the tasks assessed, appear to develop normally.

Abnormal lipid profile and hyperinsulinaemia after a mixed meal: additional cardiovascular risk factors in young adults born preterm.

AIMS/HYPOTHESIS: Low birthweight in infants born at term is related to the presence of the metabolic syndrome as an adult. Individuals born preterm invariably have low birthweights and may develop the metabolic syndrome as well. Although high BP, glucose intolerance and insulin resistance have been documented, dyslipidaemia has never been reported in individuals born preterm. METHODS: In three groups of young adults [29 participants from the POPS (Project On Premature and Small for Gestational Age Infants) cohort born preterm appropriate for gestational age (POPS-AGA), 28 participants from the POPS cohort born preterm small for gestational age (POPS-SGA) and 30 individuals born at term with normal birthweight (CON)] we investigated fasting lipids as well as postprandial responses during a mixed meal test. The relationship between fasting and postprandial measurements and insulin sensitivity, measured by the hyperinsulinaemic clamp, was investigated. RESULTS: Preterm participants had higher BP than CON individuals. Postprandial triacylglycerol levels were increased in POPS-SGA men. POPS-SGA individuals were hyperinsulinaemic during the mixed meal test. CONCLUSIONS/INTERPRETATION: The mixed meal test provides additional information on cardiovascular risk factors. Postprandial triacylglycerol levels are increased in POPS-SGA men. Postprandial hyperinsulinaemia is found in POPS-SGA individuals.

Decreased insulin sensitivity in small for gestational age males treated with GH and preterm untreated males: a study in young adults.

BACKGROUND: Low birth weight and preterm birth are associated with growth delay as well as the development of insulin resistance. Insulin resistance is especially seen in subjects with catch-up growth. GH therapy induces growth in short subjects with low birth weight at term, but little is known about the long-term effects on insulin sensitivity. GH therapy is now also proposed for preterms that remain short. METHODS: We investigated insulin sensitivity using the gold standard hyperinsulinemic-euglycemic clamp technique in 10 young adult males born small for gestational age (SGA) who had been treated with GH during childhood (GH) in comparison with 15 males born preterm AGA (premAGA), 13 males born preterm SGA (premSGA), and 15 males born at term with normal birth weight (CON). Furthermore, we investigated the presence of the metabolic syndrome. RESULTS: Insulin sensitivity was decreased in premAGA, premSGA, and GH subjects compared with CON males. The metabolic syndrome was not present in any of the groups. CONCLUSION: Insulin sensitivity is decreased in GH-treated SGA born males as well as in preterm born males. With respect to the SGA subjects, whether the difference results from perinatal-, postnatal-, or GH therapy-related factors are not known. With respect to the preterm born subjects, close surveillance is needed when commencing GH therapy.