Risk factors for the development and progression of retinopathy of prematurity in preterm infants in Indonesia.

BACKGROUND: Risk factors other than supplemental oxygen might play a role in the development of retinopathy of prematurity (ROP). In Indonesia ROP occurs in infants up to 34 weeks and 2000 g. Risk factors for the development of ROP in Indonesian NICUs have not been evaluated. Our aim was to identify other risk factors than the use of oxygen in the development and progression of ROP in preterm infants in Indonesia. METHODOLOGY: Data on 98 preterm infants with ROP and 77 controls were collected from four NICUs and two eye centers in Jakarta, Indonesia, between 2009 and 2014. We used multivariate logistic regression analysis to determine the relationship between infants and environmental variables and the development and progression of ROP. We obtained variables for ROP severity by using Cox regression analysis. RESULTS: Factors associated with the development of ROP were birthweight (BWt), intrauterine growth retardation (IUGR), exchange transfusion, duration of oxygen supplementation, minimum saturation monitor setting, and socioeconomic factors. Regarding the progression, gestational age (GA), out-born, duration of supplemental oxygen, minimum saturation monitor setting, and socioeconomic factors were identified as risk factors. CONCLUSION: The use and control of supplemental oxygen are the main risk factors for the development and progression of ROP in preterms in Indonesia. Additionally, we confirm that GA, BWt, and IUGR are risk factors. Moreover, we found exchange transfusion to be a risk factor, and we found a lower rate of ROP in infants from a lower socioeconomic background. These risk factors apply to infants with a GA up to 34 weeks and a BWt up to 2000 g.

[Mothers in the Netherlands do not have to feel guilty about bottle-feeding their babies]. / Nederlandse moeder hoeft zich niet schuldig te voelen als zij flesvoeding geeft.

Human milk provides optimal nutrition for the term new-born infant. This milk might give the infant certain advantages over formula milk, and the potential advantages are reviewed in this commentary. It is concluded that there are advantages to breastfeeding, but that these are limited for an infant in an industrialised country receiving adequate formula milk. Breastfeeding should be encouraged, but there is insufficient reason for a mother who either is not able or not willing to breastfeed to feel guilty about not doing so.

A multidisciplinary intervention programme has positive effects on quality of life in overweight and obese preschool children.

AIM: Up to 18.1% of Dutch children aged 3-5 are overweight and up to 3.3% are obese, with higher levels in girls. This study assessed the effect of a multidisciplinary intervention programme on health-related quality of life (HRQoL) in this patient group. METHODS: We randomised 75 children to a multidisciplinary intervention, comprising dietary advice, exercise sessions and psychological counselling for parents or the standard care programme, providing healthy lifestyle advice. The parents completed quality of life and child health questionnaires at baseline and after 16 weeks and 12 months. RESULTS: At 16 weeks, children in the intervention group experienced more bodily pain and less mental health than the standard care group, but at 12 months, this difference disappeared and they showed a more positive change in HRQoL than the standard care group, especially for the physical domain. When we combined both groups, a decreased BMIz-score over 12 months was associated with increased global health and reduced visceral fat correlated with increased general health. CONCLUSION: At 12 months, a multidisciplinary intervention programme for overweight and obese children aged 3-5 years had beneficial effects on HRQoL, especially for the physical domain. Reduced obesity parameters correlated with several increased HRQoL parameters.

Effects of paternal and maternal lifestyle factors on pregnancy complications and perinatal outcome. A population-based birth-cohort study: the GECKO Drenthe cohort.

STUDY QUESTION: Do paternal and maternal lifestyle factors influence the risk of hypertensive pregnancy complications, gestational diabetes mellitus (GDM), spontaneous preterm birth and small-for-gestational-age (SGA)? SUMMARY ANSWER: Paternal lifestyle factors do not exert an independent effect on the investigated outcomes while maternal prepregnancy BMI and maternal smoking during pregnancy influence the risk of hypertensive pregnancy complications, GDM and SGA. WHAT IS KNOWN ALREADY: Maternal lifestyle factors are associated with perinatal complications, but the impact of paternal lifestyle factors is unclear. STUDY DESIGN, SIZE, DURATION: Data from the GECKO (Groningen Expert Center for Kids with Obesity) Drenthe cohort, a prospective population-based birth-cohort of children born between April 2006 and April 2007 in a northern province of The Netherlands, were analysed. The parents of 2958 children (62% of those approached) gave their consent to participate in the study and the data of 2264 (77%) couples were available for analysis. PARTICIPANTS/MATERIALS, SETTINGS, METHOD: All pregnant women in the Dutch province of Drenthe with an expected date of delivery between April 2006 and April 2007 were invited to participate and included during the third trimester of their pregnancy or within 6 months after delivery. All consenting couples received extensive questionnaires including lifestyle, biological and socio-demographic-related questions covering the period of 6 months prior to conception. Outcome data were obtained from midwives and hospital registries. Univariable and multivariable logistic regression analyses were used to determine the impact of the lifestyle factors on the primary outcome measures. MAIN RESULTS AND THE ROLE OF CHANCE: Of all 2264 women, 241 women (10.6%) developed a hypertensive pregnancy complication, 50 women (2.2%) developed GDM, 79 (3.5%) children were spontaneously delivered preterm and 155 children (6.8%) were SGA. All paternal and maternal lifestyle factors were positively correlated. Multivariable analysis showed that paternal lifestyle factors did not have an independent influence on the investigated outcomes. Of the maternal factors, prepregnancy BMI was independently associated with an increased risk of a hypertensive disorder during pregnancy (odds ratio (OR): 1.12, 95% CI 1.09-1.16), a higher risk of GDM (OR BMI >23 kg/m(2), per BMI unit: 1.13, 95% CI 1.08-1.18) and with a decreased risk of SGA (OR per BMI point 0.94, 95% CI 0.90-0.99). Maternal smoking during pregnancy was significantly associated with SGA (OR 3.00, 95% CI 1.80-4.99) in multivariable analysis. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the questionnaire may have induced recall bias. Selection bias might have occurred, as ethnic minorities were less willing to co-operate in the GECKO Drenthe study. The possibility of misclassification bias regarding the primary outcome measures cannot be ruled out. Inclusion bias might have occurred as not all questionnaires of the parents of the children participating in the GECKO Drenthe cohort were completed. WIDER IMPLICATIONS OF THE FINDINGS: Paternal lifestyle factors do not have an independent effect on the investigated adverse pregnancy outcomes. However, as paternal and maternal lifestyles are positively correlated, both partners should be involved in preconception counselling regarding the investigated outcome measures.

Skipping breakfast and overweight in 2- and 5-year-old Dutch children-the GECKO Drenthe cohort.

Skipping breakfast is associated with higher BMI in children aged 5 years and older. However, not much is known about this association in younger children. In the Dutch GECKO Drenthe birth cohort we examined the association between breakfast skipping and objectively measured overweight at the age of 2 (n=1488) and 5 (n=1366) years. At 2 years, 124 (8.3%) children were overweight and 44 (3.0%) did not eat breakfast daily. At 5 years, 180 (13.2%) children were overweight and 73 (5.3%) did not eat breakfast daily. Children belonging to families of non-Dutch origin, those with lower educated parents and those with single parents skipped breakfast more often. Breakfast skipping in 2- and 5-year-olds is rare in the Netherlands. We found no association between skipping breakfast and overweight, neither at age 2 (odds ratio (OR): 1.85 (95% confidence interval (CI): 0.61-5.64)) nor at age 5 (OR: 0.46 (95% CI: 0.19-1.11)). Also the type of breakfast was not related to overweight at 5 years. An explanation for this finding might be that skipping breakfast is not (yet) an issue in these children.

Cytokines patterns in newborn infants with late onset sepsis.

BACKGROUND: Cytokines might be helpful to diagnose late onset sepsis (LOS) in newborn infants. Many studies on cytokines did not discriminate culture-proven from clinically-suspected sepsis; however, such differentiation is clinically useful. OBJECTIVES: To evaluate the feasibility to differentiate among culture-proven LOS, clinical LOS and controls using a battery of cytokines. STUDY DESIGN: This prospective study was conducted at the NICU of Harapan-Kita Women and Children's Hospital, Jakarta-Indonesia. Three groups of infants with postnatal age >72 hours of age were enrolled in the study: culture-proven sepsis group (PS) (n = 18), clinical sepsis group (CS) (n = 25) and control group (n = 34). A battery of 25 cytokines was measured in each infant five times: at enrollment, after 4 hrs, 12 hrs, 24 hrs, and 48 hrs using Invitrogen-immunoassays-Luminex™100. RESULTS: There were no significant differences in gestational age or mode of delivery among the three groups. IL-1ß, IL-2r, IL-6, IL-8, IL-10 and MIP-1a were significantly higher at all measurement points in group PS compared to controls. IL-13 was lower at all measurement moments in group CS compared to controls, IL-12 was lower and IP-10 higher between 0 and 24 hrs. IL-1Ra, IL-6, IL-8, IL-13, IL-15, TNFα, MIP-1a and MIP-1b were higher at all the measurement moments in group PS compared to group CS. The ROC curves show that IL-6, IL-8, IL-15, MIP-1a, MIP-1b and TNFα have a sensitivity and specificity between 80 and 85% during the first 24-48 hours after the onset of infection. IL-6, IL-15, MIP-1a, MIP-1b and TNFα showed the best likelihood ratios. CONCLUSIONS: IL-6, IL8, IL 15, MIP-1a, MIP-1b and TNFα are potentially good markers for detecting a proven LOS. In case these cytokines are not elevated in sick infants, other causes than an infection have to be identified.

Medical practice and legal background of decisions for severely ill newborn infants: viewpoints from seven European countries.

AIM: To comparing attitudes towards end-of-life (EOL) decisions in newborn infants between seven European countries. METHODS: One paediatrician and one lawyer from seven European countries were invited to attend a conference to discuss the practice of EOL decisions in newborn infants and the legal aspects involved. RESULTS: All paediatricians/neonatologists indicated that the best interest of the child should be the leading principle in all decisions. However, especially when discussing cases, important differences in attitude became apparent, although there are no significant differences between the involved countries with regard to national legal frameworks. CONCLUSION: Important differences in attitude towards neonatal EOL decisions between European countries exist, but they cannot be explained solely by medical or legal reasons.

Influence of prenatal organohalogen levels on infant male sexual development: sex hormone levels, testes volume and penile length.

BACKGROUND: Prenatal exposure to endocrine disruptors, like organohalogen compounds (OHCs), might be responsible for the increased aberrations in human male sexual development (hypospadias, cryptorchidism, testicular cancer and fall in sperm count) observed over the past decades. This development is established during fetal life, and reflected in sex hormone levels, testes volume and penile length post-partum. The present study investigates the correlation between prenatal OHC levels and male sexual development outcomes. METHODS AND RESULTS: Levels of eight neutral [2,2'-bis-(4-chlorophenyl)-1,1'-dichloroethene (4,4'-DDE), 2,2',4,4',5,5'-hexachlorobiphenyl, 2,2',4,4'-tetrabromodiphenyl ether (BDE)-47, -99, -100, -153, -154 and 1,2,5,6,9,10-hexabromocyclododecane, HBCDD] and four phenolic [(pentachlorophenol (PCP), 4OH-CB-107 (4-hydroxy-2,3,3',4',5-pentachlorobiphenyl), -146 and -187)] OHCs were determined in 55 maternal serum samples taken at 35 weeks of pregnancy. Eight sex development-related hormones [testosterone, free testosterone, sex hormone-binding globulin (SHBG); LH, FSH, estradiol (E(2)), free E(2) (FE(2)) and inhibin B (InhB)] were determined in their sons at 3 months of age, and testes volume and penile length at 3 and 18 months of age. The following prenatal OHC levels correlated significantly with sex hormone levels: PCP with SHBG and InhB (ρ = 0.30 and -0.43, respectively), 4OH-CB-107 with testosterone (ρ = 0.31) and BDE-154 with FE(2), E(2) and InhB (ρ = 0.49, 0.54 and 0.34, respectively). BDE-154 levels correlated positively with testes volume at 18 months of age (ρ = 0.34). CONCLUSIONS: Prenatal OHC exposure is correlated with aspects of sexual development outcome in boys up to 18 months of age.

The influence of maternal and paternal factors on time to pregnancy--a Dutch population-based birth-cohort study: the GECKO Drenthe study.

BACKGROUND: Both maternal and paternal factors have been suggested to influence a couple's fecundity. To investigate this, we examined the role of several maternal and paternal lifestyle and socio-demographic factors as determinants of time to pregnancy (TTP) in a Dutch birth-cohort. METHODS: Groningen Expert Center for Kids with Obesity (GECKO) Drenthe is a population-based birth-cohort study of children born between April 2006 and April 2007 in Drenthe, a province of The Netherlands. Both partners received extensive questionnaires during pregnancy. Univariable and multivariable Cox regression analyses were used to determine the impact of the investigated factors on TTP. RESULTS: A total of 4778 children were born, and the parents of 2997 children (63%) gave their consent to participate. After excluding unintended pregnancies and pregnancies as a result of fertility treatment, the data of 1924 couples were available for analysis. Hazards ratios and 95% confidence intervals of factors influencing TTP in multivariable Cox regression analysis were: maternal age 1.23 (0.98-1.54) for age <25 years, 1.17 (1.03-1.32) for age 25-30 years and 0.72 (0.61-0.85) for age >35 years (reference category: 30-35 years); paternal age: 1.31 (0.94-1.82) for age <25 years, 1.11 (0.97-1.28) for age 25-30 years and 0.91 (0.80-1.04 for age >35 years (reference category: 30-35 years); nulliparity: 0.76 (0.68-0.85) versus multiparity; menstrual cycle length: 1.12 (0.95-1.30) for 3 weeks, 0.72 (0.62-0.83) for 4-6 weeks, 0.68 (0.40-1.16) for >6 weeks and 0.66 (0.54-0.81) for irregular cycle (reference category: 4 weeks); prior contraceptive use: 0.78 (0.67-0.91) for no contraception, 1.68 (1.45-1.95) for condom use, 1.08 (0.89-1.33) for condom use combined with oral contraception, 1.40 (1.16-1.70) for intrauterine device and 0.50 (0.25-1.01) for contraceptive injection (reference category: oral contraception); and maternal educational level 0.75 (0.62-0.92) for low education level and 0.81 (0.73-0.90) for medium educational level (reference category: high educational level). CONCLUSIONS: This population-based birth-cohort study performed in fertile couples who had conceived revealed neither maternal nor paternal modifiable lifestyle factors were significantly associated with TTP after adjustment for confounding by socio-demographic factors. In contrast, several non-modifiable maternal socio-demographic factors are significant predictors of a couple's fecundity.

Metabolic responses to long-term pharmacological inhibition of CB1-receptor activity in mice in relation to dietary fat composition.

BACKGROUND AND OBJECTIVES: The antiobesity effects of suppressed endocannabinoid signaling may rely, at least in part, on changes in lipid fluxes. As fatty acids exert specific effects depending on their level of saturation, we hypothesized that the dietary fatty acid composition would influence the outcome of treatment with a CB(1)-receptor antagonist (rimonabant). METHODS: Mice were treated with rimonabant (10 mg kg(-1) body weight per day) or vehicle while equicalorically fed either a low-fat diet (LF), a high-fat (HF) diet or an HF diet in which 10% of the saturated fatty acids (SFAs) were replaced by poly-unsaturated fatty acids (PUFA) from fish oil (FO). Food intake and body weight were registered daily. Indirect calorimetry was performed and feces were collected. After 3 weeks, mice were killed for blood and tissue collection. RESULTS: Relative to the LF diet, the HF diet caused anticipated metabolic derangements, which were partly reversed by the HF/FO diet. The HF/FO diet, however, was most obesity-promoting despite inhibiting lipogenesis as indicated by low gene expression levels of lipogenic enzymes. On all three diets, rimonabant treatment improved metabolic derangements and led to significantly lower body weight gain than their respective controls. This latter effect appeared largest in the HF/FO group, but occurred without major changes in nutrient absorption and energy expenditure. CONCLUSION: The effects of chronic rimonabant treatment on body weight gain occurred irrespective of diet-induced changes in lipogenic activity, food intake and daily energy expenditure, and were, in fact, most pronounced in HF/FO mice. The effects of dietary PUFA replacement in an HF diet on expansion of adipose tissue might allow the favorable effects of dietary PUFA on dyslipidemia and hepatic steatosis. In light of other disadvantageous effects of weight gain, this might be a risky trade-off.

How do parents of 4- to 5-year-old children perceive the weight of their children?

INTRODUCTION: A heavier weight in adults is becoming the norm rather than an abnormal weight. Whether the same trend is happening in children is unknown. OBJECTIVE: To assess the perception of the weight of 4- to 5-year-old children and the recognition of overweight by both parents. DESIGN: Population-based survey. PARTICIPANTS: A questionnaire was sent to parents of 1155 4- to 5-year-old children. RESULTS: In total, 439 questionnaires (35%) were returned. Of all, 90% of the children had a normal weight, 9.3% were overweight and 4.1% were obese. For all weight classes, the parents depicted the child as lighter on both the verbal and visual scale. Of all, 75% of mothers of overweight children stated that the child had a normal weight. In obese children, 50% of the mothers believed that the child had a normal weight. CONCLUSION: Children with a weight in the normal range were considered by their parents as a little too light or too light. Overweight was considered as normal weight, and obesity as normal or a little too heavy. The perception of a normal weight in children at 4-5 years is distorted.

Measuring abdominal adiposity in 6 to 7-year-old children.

BACKGROUND/OBJECTIVES: Both intra-abdominal adipose tissue (IAAT) and subcutaneous abdominal adipose tissue (SAAT) are associated with cardiovascular risk factors, even in childhood. Currently, the gold standard in assessing IAAT and SAAT is computed tomography (CT), which is not widely applicable. The aim of this study was to estimate abdominal fat using anthropometry, dual-energy X-ray absorptiometry (DEXA) and ultrasound, and compare these estimates with the amounts of IAAT and SAAT determined by CT in 6 to 7-year-old children. SUBJECTS/METHODS: In 31 healthy children, weight, height, circumferences, skinfolds, DEXA, abdominal ultrasound and CT were performed. Measurements were compared by simple correlations and receiver operating characteristic analyses. RESULTS: Total abdominal fat on CT did not differ between boys and girls (86.5 versus 89.8 cm(3), P=0.84). Boys had a higher IAAT to SAAT ratio than girls (0.56 versus 0.37, P=0.03). The sum of supra-iliac and abdominal skinfolds was most strongly correlated with SAAT on CT (r=0.93, P<0.001), and the abdominal skinfold with IAAT on CT (r=0.72, P<0.001). Diagnosis of subcutaneous abdominal and intra-abdominal adiposity can also be made using skinfolds. The associations with circumferences, body mass index and DEXA were less pronounced; however, these techniques can also be used to classify children according to SAAT and IAAT. Ultrasound can be used to diagnose subcutaneous adiposity, although it was not superior to skinfold measurements. CONCLUSION: Skinfold measurements are the best non-invasive technique in predicting subcutaneous as well as intra-abdominal fat in our population of 6 to 7-year-old children.

[Non-alcoholic fatty liver disease in children: a new complication of obesity]. / 'Non-alcoholic fatty liver disease' bij kinderen: een nieuwe complicatie van obesitas.

Non-alcoholic fatty liver disease (NAFLD) comprises a range of chronic liver diseases from simple steatosis to steatohepatitis and cirrhosis with liver failure. In children, NAFLD is mainly associated with obesity and metabolic syndrome, the results of an unhealthy lifestyle. Insulin resistance and free fatty acids play a key role in the pathogenesis of NAFLD. NAFLD can therefore be seen as a metabolic complication of obesity. Since the prevalence of obesity in Dutch children is increasing, the prevalence of NAFLD in children is expected to increase as well. Prevention of obesity and identification of children with an increased risk of NAFLD are important steps in preventing irreversible liver damage. Lifestyle changes aimed at improving insulin sensitivity through healthy food and sufficient physical activity are essential in the treatment of NAFLD. Pharmacological treatment may have additional value.

Movement analysis in neonates with spina bifida aperta.

INTRODUCTION: In neonates with spina bifida aperta (SBA), leg movements by myotomes caudal to the meningomyelocele (MMC) are transiently observed. It is unclear whether these leg movements relate to functional neural conduction through the MMC. For optimal therapeutical intervention, pathophysiological insight in these transient leg movements seems relevant. If leg movements by myotomes caudal to the MMC concur with the execution of general movements (GMs), functional neural conduction through the MMC is implicated. OBJECTIVE: In neonates with SBA, we aimed to determine whether the transiently present leg movements caudal to the MMC indicate functional neural conduction through the MMC. METHODS: During the perinatal period, fetuses and neonates with SBA (n = 7 and n = 13, respectively) were longitudinally analysed for concurrency between leg movements caudal to the MMC and GMs. To address the integrity of the reflex arc in spinal segments (at, or) caudal to the MMC, tendon leg reflexes were assessed during the first postnatal week. RESULTS: At postnatal day 1, leg movements caudal to the MMC concurred with GMs in 12 of 13 infants. Isolated leg movements were observed in only 3 of these 12 infants (isolated vs. concurrent; p < 0.005). Leg movements concurring with GMs lasted longer than isolated leg movements (median duration = 11 s vs. 2 s; p < 0.05). Between days 1 and 7, tendon leg reflexes (at, or) caudal to the MMC had disappeared in all but 1 neonate. However, leg movements caudal to the MMC remained concurrently present with GMs in all five neonates available for follow-up after day 7. Comparing these leg movements between days 1 and 7 indicated a decreased duration (-44%, p < 0.05). CONCLUSIONS: In neonates with SBA, leg movements caudal to the MMC concur with GMs, indicative of functional neural conduction through the MMC. The disappearance of these leg movements is caused by lower motor neuron dysfunction at the reflex arc, whereas neural conduction through the MMC is still functional.

End-of-life decisions in newborns: an approach from The Netherlands.

End-of-life decisions in newborns with incurable conditions are especially difficult for pediatricians if they regard the group of stable infants with a hopeless prognosis, not dependent on technology. If a life full of severe and sustained suffering that cannot be relieved by any other means is expected, deliberate ending of life can be an acceptable choice in the Netherlands under very strict conditions. To increase the quality of the decision-making process and facilitate the mandatory reporting of life-ending procedures, a set of medical and legal guidelines (the Groningen protocol) was made in our institution in collaboration with the district attorney. This protocol serves as a tool to bring newborn euthanasia under a regime of effective control. This article describes the present approach to life-ending measures in newborns in the Netherlands and gives an overview of the protocol.

Ethical and practical issues regarding research in children: the European perspective.

Children, like all humans, are exposed to compounds in the environment and sometimes to drugs. The effect of this exposure cannot simply be deducted from studies in adults or animals. Effects might be different and even more dramatic than in adults due to the stage of growth and development of the infant. Around 80% of drugs used in young individuals are not licensed for use in this age group. Almost three new chemical compounds enter the environment each day. Toxicological studies in infants and children therefore are needed and ethically acceptable. However, appropriate safeguards must be taken into account. According to the Good Clinical Practice Directive of the European Parliament (2001/20) not only therapeutic, but also non-therapeutic research in infants and children is allowed, provided the study can only be conducted in children, and the results of the study in children will be of benefit to the group represented and no more than minimal harm and risk is inflicted to the children. Many more toxicological studies are needed in children and infants. Not conducting these studies is detrimental for this age group.