Predictors and consequences of non-suicidal self-injury in relation to life, peer, and school factors.

INTRODUCTION: Numerous life, peer, and school-related factors have been found to be associated with non-suicidal self-injury (NSSI) among adolescents; however, most studies have not explored the possible reciprocal nature of these associations. The aim of the current study was to examine bidirectional and longitudinal associations between NSSI and several life, peer, and school-related factors (i.e., stressful life events, peer relationships, academic achievement, and attitudes towards school). METHOD: Community-based adolescents completed questionnaires assessing the variables of interest at three time points; age 12 (T1; 55.09% girls), age 13 (T2; 56.95% girls), and ages 14-15 (T3; 57.41% girls). In total, 529 adolescents provided complete data across all three-time points. RESULTS: Analyses showed a bidirectional association between NSSI and both attitudes towards school and stressful life events. Specifically, stressful life events at T2 predicted engagement in NSSI at T3, and NSSI at T2 predicted increased risk of stressful life events at T3. Similarly, having negative attitudes towards school predicted NSSI at T2, which, in turn, predicted negative attitudes towards school at T3. Further, academic achievement at T1 was negatively associated with NSSI at T2. Peer relationships were neither a predictor nor a consequence of NSSI. CONCLUSIONS: Our results suggest that NSSI can be both a predictor and a consequence of various life, and school factors. Focus on these factors in prevention and intervention efforts for NSSI among adolescents may be warranted.

Chromosomal abnormalities after ICSI in relation to semen parameters: results in 1114 fetuses and 1391 neonates from a single center.

STUDY QUESTION: Is there a relationship between karyotype abnormalities in fetuses and children conceived by ICSI and their father's semen parameters? SUMMARY ANSWER: The de novo chromosomal abnormality rate in pre- and postnatal karyotypes of ICSI offspring was higher than in the general population and related to fathers' sperm parameters. WHAT IS KNOWN ALREADY: Several studies have reported a higher rate of de novo chromosomal anomalies in ICSI fetuses but recent data from large cohorts are limited. Overall, reported prevalences of non-inherited karyotype aberrations are increased in fetuses conceived after ICSI and vary between 1.6% and 4.2%. Only a few studies focus on the relation between karyotype anomalies in ICSI offspring and semen parameters of their fathers. Furthermore, an increased incidence of abnormal karyotypes in ICSI neonates has been described, but the rates vary widely across studies. STUDY DESIGN, SIZE, DURATION: We report on karyotype results from prenatal testing by means of chorionic villus sampling and amniocentesis and results from postnatal blood sampling in offspring conceived by ICSI in a single center. Ongoing pregnancies resulting from an oocyte retrieval between January 2004 and December 2012 and after transfer of fresh ICSI embryos obtained using ejaculated or non-ejaculated sperm (fresh or frozen-thawed) were considered. Pregnancies following frozen embryo transfer, oocyte or sperm donation, IVF, preimplantation genetic testing and IVM were excluded. All abnormal prenatal results after sampling are reported irrespective of the outcome of the pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: From the 4816 ongoing ICSI pregnancies, information on pregnancy outcome was available for 4267 pregnancies. Prenatal testing was performed in 22.3% of the pregnancies, resulting in a diagnosis in 1114 fetuses. A postnatal karyotype was obtained in 29.4% of the pregnancies in which no invasive prenatal diagnosis was performed, resulting in a total of 1391 neonates sampled. The prevalence of chromosomal anomalies according to maternal age and semen quality was analyzed with logistic regression. For definitions of normal semen quality, the World Health Organization reference values for human semen characteristics were adopted. MAIN RESULTS AND THE ROLE OF CHANCE: An abnormal fetal karyotype was found in 29 singletons and 12 multiples (41/1114; 3.7%; 95% CI 2.7-4.9%): 36 anomalies were de novo (3.2%; 95% CI 2.3-4.4), either numerical (n = 25), sex (n = 6) or structural (n = 5), and five were inherited. Logistic regression analysis did not show a significant association between maternal age and a de novo chromosomal fetal abnormality (odds ratio (OR) 1.05; 95% CI 0.96-1.15; P = 0.24). In all but one case, fetuses with an abnormal karyotype were conceived by ICSI using ejaculated sperm.Abnormal karyotypes were found in 14 (1.0%; 95% CI 0.6-1.7) out of 1391 postnatal samples of children born after ICSI who were not tested prenatally: 12 were de novo anomalies and two were inherited balanced karyotypes. The 14 abnormal karyotypes were all found in children born after ICSI using ejaculated sperm.The odds of a de novo karyotype aberration increased with maternal age when combining pre- and postnatal data (OR 1.11; 95% CI 1.04-1.19). A higher rate of de novo chromosomal abnormalities was found in fetuses and children of couples with men having a sperm concentration <15 million/ml (adjusted OR (AOR) 2.10; 95% CI 1.14-3.78), sperm concentration <5 million/ml (AOR 1.9; 95% CI 1.05-3.45) and total sperm count <10 million (AOR 1.97; 95% CI 1.04-3.74). LIMITATIONS, REASONS FOR CAUTION: We cannot exclude that the observation of a higher prevalence of karyotype anomalies in ICSI offspring compared to literature data in the general population is due to enhanced surveillance after ART given the lack of a control group. Although we did not find more chromosomal anomalies after ICSI with non-ejaculated sperm, the small numbers do not allow firm conclusions. WIDER IMPLICATIONS OF THE FINDINGS: The observed increased risk of a de novo karyotype anomaly after ICSI conception in couples with poor sperm warrants continued counseling toward prenatal testing.The current and widespread use of innovative non-invasive prenatal testing will result in larger datasets, adding to a balanced estimation of the prevalence of karyotype anomalies in ICSI offspring. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Methusalem grants issued by the Vrije Universiteit Brussel. All authors declared no conflict of interest related to this study. TRIAL REGISTRATION NUMBER: N/A.

Metabolic Syndrome and Its Components in Young Adults Conceived by ICSI.

BACKGROUND: Intracytoplasmic sperm injection (ICSI) conception presents the early embryo with a radically different environment, which may lead to permanent alterations to key cardiometabolic processes. Blood pressure, indicators of insulin resistance, and lipid profiles have previously been studied in offspring born after in vitro fertilisation (IVF) and ICSI, with conflicting findings. Also, results in young adults born after ICSI are lacking. AIM: We investigated if young adult men and women conceived by ICSI more frequently have metabolic syndrome and its individual features in comparison to spontaneously conceived controls. DESIGN: Cardiometabolic and anthropometric parameters from 126 longitudinally followed young adults conceived by ICSI were compared to those of 133 controls. RESULTS: At age 18 years, only 1 of the participants displayed the metabolic syndrome (1 control woman). Mean concentrations of total cholesterol, triglycerides, insulin, HOMA-IR, and blood pressure were comparable between the ICSI conceived and control participants. A higher proportion (19.6%) of men conceived by ICSI had low (<40 mg/dl) HDL cholesterol compared to controls (5.6%). CONCLUSIONS: While men conceived by ICSI, but not women, had lower mean HDL cholesterol concentrations in comparison to controls, other markers of the metabolic syndrome were not affected by the mode of conception.

Adult Height after Growth Hormone Treatment at Pubertal Onset in Short Adolescents Born Small for Gestational Age: Results from a Belgian Registry-Based Study.

OBJECTIVES: Information on the efficacy of GH treatment in short SGA children starting their treatment in adolescence is limited. Therefore, adult height (AH), total height gain, and pubertal height gain were evaluated in short SGA children who started GH treatment at pubertal onset. PATIENT AND METHODS: Growth data of 47 short SGA adolescents (22 boys) who started GH treatment at pubertal onset (PUB group) were compared with results from 27 short SGA patients (11 boys) who started GH therapy at least 1 year before pubertal onset (PrePUB group). RESULTS: The PUB group achieved a mean (±SD) total height gain of 0.8 ± 0.7 SDS and an AH of -2.5 ± 0.7 SDS after 4.1 ± 1.1 years of GH treatment with a dosage of 41.8 ± 8.4 µg/kg/day. These results were comparable with those in the PrePUB group, which was treated for a longer duration (5.8 ± 2.1 years), resulting in a total height gain of 1.1 ± 0.7 SDS and an AH of -2.1 ± 1.0 SDS. Multiple regression analysis showed a significantly lower height gain in pubertal patients, females, and patients weighing less at start of GH treatment. An AH above -2 SDS and above the parent-specific lower limit of height was, respectively, reached in 28% and 70% of PUB and 44% and 67% of PrePUB patients (NS). AH SDS was positively correlated with the height SDS at start of GH. CONCLUSIONS: Short SGA adolescents starting GH therapy at an early pubertal stage have a modest and variable height gain. A normal AH can be expected in one third of the patients, especially in those with a smaller height deficit at onset of GH treatment.

Can Flanders resist the measles outbreak? Assessing vaccination coverage in different age groups among Flemish residents.

The Belgian strategic plan to eliminate measles contains several vaccination strategies including routine immunisation programmes and catch-up campaigns. A new expanded programme on immunisation-based survey (2016) assessed the uptake of the recommended measles-mumps-rubella (MMR) vaccine in three different cohorts: toddlers, adolescents and parents of toddlers. A two-stage cluster sampling technique was used to select 875 toddlers (age 18-24 months) and 1250 adolescents (born in 2000) from 107 municipalities in Flanders. After consent of the parent(s), 746 (85.2%) families of toddlers and 1012 (81.0%) families of adolescents were interviewed at home. Measles vaccination coverage was high at 18-24 months (96.2%) and 81.5% were vaccinated at recommended age. Toddlers who had two siblings or a non-working mother or changed vaccinator were more at risk for not being vaccinated. Coverage of the teenager dose reached 93.5% and was lower in adolescents with educational underachievement or whose mother was part-time working or with a non-Belgian background. Only 56.0% of mothers and 48.3% of fathers remembered having received at least one measles-containing vaccine. Although measles vaccination coverage in toddlers meets the required standards for elimination, administration of the teenager dose of MMR vaccine and parent compliance to the recent measles catch-up campaign in Flanders leave room for improvement.

Body fat content, fat distribution and adipocytokine production and their correlation with fertility markers in young adult men and women conceived by intracytoplasmic sperm injection (ICSI).

OBJECTIVE: Differences in body fat content during childhood and adolescence have been described in offspring conceived by in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). However, data on body fat and its distribution as well as on adipocytokine production in young adults conceived by ICSI are nonexistent. We investigated if young adult men and women conceived by ICSI have a normal body fat patterning and adipocytokine production. DESIGN: Cohort study. PATIENTS: One hundred twenty-seven young adults conceived by ICSI and 138 peers born after spontaneous conception. MEASUREMENTS: Anthropometric parameters (skinfold thickness, hip and waist circumferences), dual X-ray absorptiometry (whole body and regional) measurements and adipocytokine levels (leptin and adiponectin) were analysed in relation to fertility markers (serum anti-Mullerian hormone (AMH) and inhibin B). RESULTS: While at age 18 years, a normal body fat distribution and normal leptin and adiponectin production was found in both male and female ICSI offspring, young men conceived by ICSI had a higher peripheral fat deposition in comparison with spontaneously conceived peers. No correlation between AMH and inhibin B with leptin or adiponectin was observed. CONCLUSION: While men conceived by ICSI, but not women, had a higher peripheral fat deposition, body fat distribution as well as mean levels of adipocytokines were not affected by the mode of conception.

Body composition and blood pressure in 6-year-old singletons born after pre-implantation genetic testing for monogenic and structural chromosomal aberrations: a matched cohort study.

STUDY QUESTION: Does Day 3 embryo biopsy for pre-implantation genetic testing for monogenic (PGT-M) and structural chromosomal aberrations (PGT-SR) affect body composition and blood pressure readings of 6-year-old singletons? SUMMARY ANSWER: This study of 87 PGT-M and PGT-SR conceived singletons showed no differences in anthropometric measurements and blood pressure readings in comparison with a matched cohort of peers born after ICSI without embryo biopsy. WHAT IS KNOWN ALREADY: While neonatal outcomes after PGT conception have been found comparable to those after ICSI without embryo biopsy, only a few studies have reported outcomes after PGT at older ages. Moreover, embryo biopsy is also applied in couples who opt for PGT-M and PGT-SR and hence are not necessarily infertile. Health parameters and in particular body composition data in this group of children are lacking. STUDY DESIGN SIZE DURATION: This single-centre matched-pair cohort study evaluated body composition of 6-year-old children born after fresh blastocyst embryo transfer with or without embryo biopsy performed at Day 3 for the purpose of PGT-M and PGT-SR. For each child born after embryo biopsy, a singleton born after transfer of a fresh ICSI embryo at the blastocyst stage and reaching the age of 6 years between May 2011 and June 2017 was matched as closely as possible for gender, age, maternal educational level and birth order. PARTICIPANTS/MATERIALS SETTING METHODS: Anthropometry (weight, height, BMI, skinfold thickness, waist and mid-upper arm circumference) and blood pressure readings in a longitudinally followed cohort of 87 singletons conceived by PGT-M and PGT-SR and a pairwise matched sample of 87 children conceived by ICSI are described. Results are adjusted for current, neonatal and parental characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: From the 124 eligible PGT-M and PGT-SR families, 110 could be reached of whom 23 refused and 87 (87/110 = 79%) participated. All anthropometric measurements, including z-scores of BMI, waist and mid-upper arm circumference, were comparable between the PGT-M and PGT-SR (-0.23; 0.27; 0.17, respectively) and ICSI (-0.29; 0.11; 0.11, respectively) groups (all P > 0.05). Furthermore, indices of peripheral (triceps) and central (subscapular) adiposity derived from skinfold thickness were comparable (PGT-M and PGT-SR: 14.7 mm; 11.6 mm and ICSI: 15.5 mm; 11.5 mm) as well as the percentage total body fat mass derived from these (PGT-M and PGT-SR: 13.7% and ICSI: 13.9%) (all P > 0.05). Z-scores for blood pressure were also comparable between the PGT and ICSI groups (all P > 0.05). Results did not change when adjusted for neonatal (birthweight, birth order), current (age) and parental (smoking during pregnancy, parental BMI) characteristics. Hospitalization rate and surgical intervention rate were not different for PGT-M and PGT-SR children compared to matched peers born after ICSI. LIMITATIONS REASONS FOR CAUTION: Although our study describes the largest cohort of singletons born after embryo biopsy worldwide, we were only able to detect moderate differences in anthropometrics and blood pressure with our sample size. WIDER IMPLICATIONS OF THE FINDINGS: Although Day 3 embryo biopsy followed by blastocyst transfer is not associated with adverse outcomes regarding anthropometry and blood pressure, future studies should focus on outcomes in children born after trophectoderm biopsy and/or transfer of warmed embryos after vitrification. STUDY FUNDING/COMPETING INTERESTS: This study was supported by Methusalem grants and by grants from Wetenschappelijk Fonds Willy Gepts; all issued by the Vrije Universiteit Brussel (VUB). All co-authors, except M.B. declared no conflict of interest. M.B. has received consultancy fees from MSD, Serono Symposia and Merck. The Universitair Ziekenhuis Brussel (UZ Brussel) and the Centre for Medical Genetics have received several educational grants from IBSA, Ferring, Organon, Shering-Plough, Merck for establishing the database for follow-up research and organizing the data collection.

[Body mass index charts of Algerian children and adolescents (6-18 years)]. / Courbes de l'indice de masse corporelle d'enfants et adolescents algériens (6­18 ans).

The body mass index (BMI) is widely accepted as a measure of overweight and obesity in children. There are no BMI reference charts for Algerian children and adolescents. The purpose of this study was to construct BMI percentile curves appropriate for children aged 6-18 years in Algeria. The weight and height of 7772 (54.9% girls) healthy schoolchildren from Constantine (eastern Algeria) were measured in 2008/2009. Weight and height for age curves based on the same sample were published previously. The BMI for age percentile curves were estimated in girls and boys separately using the LMS smoothing method. In both sexes, the median BMI increased with age. Girls had lower BMI values than boys before the age of 10 years but they were higher after this age until 18 years of age. Within the study population, the prevalence of overweight (including obesity) and obesity in girls and boys together was 13.7% and 3.0%, respectively, according to the International Obesity Task Force (IOTF) and 16.9% and 4.9% according to the World Health Organization (WHO) (2007). The median BMI curves of Algerian girls and boys were generally lower than those observed in other Arab countries. Compared with other references, the median BMI values of girls were lower than those of a Belgian Flemish population and WHO 2007 until 14 years of age and higher than the French reference between 7 and 18 years of age. The BMI values of Algerian boys were close to the Belgian (Flemish population), French and WHO 2007 references between 6 and 9 years of age and generally lower thereafter. These BMI curves are complementary to the height and weight charts published previously for the assessment of growth in children and adolescents. They were developed according to international guidelines and could serve as a national reference. They could be used as a complement to the 0- to 5-year-old WHO 2006 standards.

Semen quality of young adult ICSI offspring: the first results.

STUDY QUESTION: What is the semen quality of young adult men who were conceived 18-22 years ago by ICSI for male infertility? SUMMARY ANSWER: In this cohort of 54 young adult ICSI men, median sperm concentration, total sperm count and total motile sperm count were significantly lower than in spontaneously conceived peers. WHAT IS KNOWN ALREADY: The oldest ICSI offspring cohort worldwide has recently reached adulthood. Hence, their reproductive health can now be investigated. Since these children were conceived by ICSI because of severe male-factor infertility, there is reasonable concern that male offspring have inherited the deficient spermatogenesis from their fathers. Previously normal pubertal development and adequate Sertoli and Leydig cell function have been described in pubertal ICSI boys; however, no information on their sperm quality is currently available. STUDY DESIGN, SIZE, DURATION: This study was conducted at UZ Brussel between March 2013 and April 2016 and is part of a large follow-up project focussing on reproductive and metabolic health of young adults, between 18 and 22 years and conceived after ICSI with ejaculated sperm. Results of both a physical examination and semen analysis were compared between young ICSI men being part of a longitudinally followed cohort and spontaneously conceived controls who were recruited cross-sectionally. PARTICIPANTS/MATERIALS, SETTING, METHOD: Results of a single semen sample in 54 young adult ICSI men and 57 spontaneously conceived men are reported. All young adults were individually assessed, and the results of their physical examination were completed by questionnaires. Data were analysed by multiple linear and logistic regression, adjusted for covariates. In addition, semen parameters of the ICSI fathers dating back from their ICSI treatment application were analysed for correlations. MAIN RESULTS AND THE ROLE OF CHANCE: Young ICSI adults had a lower median sperm concentration (17.7 million/ml), lower median total sperm count (31.9 million) and lower median total motile sperm count (12.7 million) in comparison to spontaneously conceived peers (37.0 million/ml; 86.8 million; 38.6 million, respectively). The median percentage progressive and total motility, median percentage normal morphology and median semen volume were not significantly different between these groups. After adjustment for confounders (age, BMI, genital malformations, time from ejaculation to analysis, abstinence period), the statistically significant differences between ICSI men and spontaneously conceived peers remained: an almost doubled sperm concentration in spontaneously conceived peers in comparison to ICSI men (ratio 1.9, 95% CI 1.1-3.2) and a two-fold lower total sperm count (ratio 2.3, 95% CI 1.3-4.1) and total motile count (ratio 2.1, 95% CI 1.2-3.6) in ICSI men compared to controls were found. Furthermore, compared to men born after spontaneous conception, ICSI men were nearly three times more likely to have sperm concentrations below the WHO reference value of 15 million/ml (adjusted odds ratio (AOR) 2.7; 95% CI 1.1-6.7) and four times more likely to have total sperm counts below 39 million (AOR 4.3; 95% CI 1.7-11.3). In this small group of 54 father-son pairs, a weak negative correlation between total sperm count in fathers and their sons was found. LIMITATIONS, REASONS FOR CAUTION: The main limitation is the small study population. Also, the results of this study where ICSI was performed with ejaculated sperm and for male-factor infertility cannot be generalized to all ICSI offspring because the indications for ICSI have nowadays been extended and ICSI is also being performed with non-ejaculated sperm and reported differences may thus either decrease or increase. WIDER IMPLICATIONS OF THE FINDINGS: These first results in a small group of ICSI men indicate a lower semen quantity and quality in young adults born after ICSI for male infertility in their fathers. STUDY FUNDING/COMPETING INTERESTS: This study was supported by Methusalem grants and by grants from Wetenschappelijk Fonds Willy Gepts, all issued by the Vrije Universiteit Brussel (VUB). All co-authors except M.B. and H.T. declared no conflict of interest. M.B. has received consultancy fees from MSD, Serono Symposia and Merck. The Universitair Ziekenhuis Brussel (UZ Brussel) and the Centre for Medical Genetics have received several educational grants from IBSA, Ferring, Organon, Shering-Plough and Merck for establishing the database for follow-up research and organizing the data collection. The institution of H.T. has received research grants from the Research Fund of Flanders (FWO), an unconditional grant from Ferring for research on testicular stem cells and research grants from Ferring, Merck, MSD, Roche, Besins, Goodlife and Cook for several research projects in female infertility. H.T. has received consultancy fees from Finox, Abbott and ObsEva for research projects in female infertility.

Neonatal health including congenital malformation risk of 1072 children born after vitrified embryo transfer.

STUDY QUESTION: Does vitrification of Day 3 and Day 5 embryos adversely affect birth outcomes of singletons and twins in comparison with peers born after fresh embryo transfer? SUMMARY ANSWER: Neonatal health parameters, including the prevalence of congenital malformations, in singletons and twins born after embryo vitrification are similar to or slightly better than after fresh embryo transfer. WHAT IS ALREADY KNOWN: Although vitrification, rather than slow-freezing, of embryos is routine practice nowadays, convincing evidence regarding the safety for the offspring is sparse. Literature data comprise results from mostly small-sized studies or studies including only Day 3 or only Day 5 vitrified embryo transfers. Overall, better or comparable perinatal outcomes, in terms of higher birthweight and lower risk for small-for-gestational age or for low birthweight, have been reported for singletons born after vitrified embryo transfer compared with fresh embryo transfer. According to the single available study with sufficient sample size, the congenital malformation rate was found to be comparable after vitrified and fresh embryo transfers. STUDY DESIGN, SIZE, DURATION: Data were collected from 960 cycles after transfer of embryos vitrified on Day 3 (n = 457) or Day 5 (n = 503) and from 1644 cycles after fresh embryo transfer on Day 3 (n = 853) or Day 5 (n = 791), performed between 2008 and 2013 at the Centre for Reproductive Medicine of the university hospital UZ Brussel. Outcome measures were neonatal health in terms of birthweight, small-for-gestational age, prematurity rate, perinatal death and major/minor/total malformation rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Perinatal health parameters of 11 stillborns and 1061 live borns (827 singletons and 234 twins) in the vitrified group and of 28 stillborns and 1838 live borns (1374 singletons and 464 twins) in the fresh embryo group are reported. Within 3 months after birth, children in the two study groups were assessed clinically with special attention to congenital malformations by a paediatrician blinded to the type of embryo transfer. Data were analysed by multiple linear and logistic regression, adjusted for treatment variables and maternal characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Mothers to infants in the vitrified group were on average slightly older and more often suffering from pregnancy-related hypertensive disorders than mothers to infants in the fresh transfer group. Singletons born after vitrification showed a higher birthweight standard deviation score (SDS) (-0.4 versus -0.7; 95% confidence interval (CI): 0.0-0.3, P = 0.001) and a lower small-for-gestational age rate (AOR: 0.55; 95% CI: 0.34-0.90) in comparison with peers born after fresh embryo transfer. Preterm birth rate and perinatal death rate were comparable between the two groups (AOR: 0.91; 95% CI: 0.57-1.43 and AOR: 0.97; 95% CI: 0.40-2.36). In twins, neonatal outcomes including birthweight SDS, small-for-gestational age and prematurity rates were comparable in the vitrified and the fresh groups, when adjusted for confounders. Furthermore, the rate of major congenital malformations in live borns was comparable between the vitrified group and the fresh group, both in singletons (2.6 versus 2.8%; AOR: 0.91; 95% CI: 0.47-1.78) and in twins (2.4 versus 2.7%; AOR: 0.51; 95% CI: 0.05-5.72). Also, the total malformation rate in the vitrified group (3.4%; 95% CI: 2.4-4.8) did not differ from the rate in the fresh embryo group (3.9%; 95% CI: 3.1-5.0). The embryonic stage at vitrification or fresh transfer (cleavage-stage embryo or blastocyst) did not influence the birth characteristics or malformation rate. LIMITATIONS, REASONS FOR CAUTION: The main limitation of this study is the rather small twin group. Therefore, the outcome results for twins should be interpreted cautiously. WIDER IMPLICATIONS OF THE FINDINGS: This study provides evidence that transfer of vitrified Day 3 and Day 5 embryos does not adversely affect the neonatal health of the offspring in comparison with transfer of fresh embryos. Furthermore, neonatal outcomes were not different after transfer of vitrified blastocysts compared with transfer of vitrified cleavage-stage embryos. STUDY FUNDING/COMPETING INTERESTS: Educational grants for establishing and organizing the data collection have come from IBSA, Ferring, Organon, Shering-Plough and Merck. Merck Belgium funded the data collection for outcomes after vitrification between 2012 and 2015. All co-authors, except M.B., declared no conflict of interest. M.B. has received consultancy fees from Organon, Serono Symposia and Merck.

Gastric emptying of solids in children: reference values for the (13) C-octanoic acid breath test.

BACKGROUND: (99m) Technetium scintigraphy ((99m) TS) is the 'gold standard' for measuring gastric emptying (GE), but it is associated with a radiation exposure. For this reason, the (13) C-octanoic acid breath test ((13) C-OBT) was developed for measuring GE of solids. The objective of this study was to determine normal values for gastric half-emptying time (t1/2 GE) of solids in healthy children. METHODS: Gastric emptying of a standardized solid test meal consisting of a pancake evaluated with (99m) TS and (13) C-OBT was compared in 22 children aged between 1 and 15 years with upper gastrointestinal symptoms. Subsequently, the (13) C-OBT was used to determine normal values for GE of the same solid test meal in 120 healthy children aged between 1 and 17 years. KEY RESULTS: The results showed a significant correlation (r = 0.748, p = 0.0001) between t1/2 GE measured with both techniques in the group of children with upper gastrointestinal symptoms. In the group of healthy children, mean t1/2 GE was 157.7 ± 54.0 min (range 71-415 min), but t1/2 GE decreased with age between 1 and 10 years and remained stable afterward. There was no influence of gender, weight, height, body mass index, and body surface area on t1/2 GE. CONCLUSIONS & INFERENCES: Normal values for GE of solids measured with the (13) C-OBT using a standardized methodology were determined in healthy children. We propose to use this method and corresponding reference ranges to study GE of solids in children with gastrointestinal problems.

[Weight and height local growth charts of Algerian children and adolescents (6-18 years of age)]. / Courbes de poids et de taille d'enfants et adolescents algériens âgés de 6 à 18 ans.

Measurements of height and weight provide important information on growth and development, puberty, and nutritional status in children and adolescents. The aim of this study was to develop contemporary reference growth centiles for Algerian children and adolescents (6-18 years of age). A cross-sectional growth survey was conducted in government schools on 7772 healthy schoolchildren (45.1% boys and 54.9% girls) aged 6-18 years in Constantine (eastern Algeria) in 2008. Height and weight were measured with portable stadiometers and calibrated scales, respectively. Smooth reference curves of height and weight were estimated with the LMS method. These height and weight curves are presented together with local data from Arab countries and with the growth references of France, Belgium (Flanders), and the World Health Organization (WHO) 2007. In girls, median height and weight increased until 16 and 17 years of age, respectively, whereas in boys, they increased through age 18 years. Between ages 11 and 13 years (puberty), girls were taller and heavier than boys. After puberty, boys became taller than girls, by up to 13 cm by the age of 18 years. Median height and weight of Algerian boys and girls were generally intermediate between those observed in other Arab countries. They were higher than the French reference values up to the age of 13 years and lower than Belgian and WHO reference values at all ages. The present study provides Algerian height- and weight-for-age growth charts, which should be recommended as a national reference for monitoring growth and development in children and adolescents.

Rotavirus vaccination coverage and adherence to recommended age among infants in Flanders (Belgium) in 2012.

In Belgium, rotavirus vaccination has been recommended and partially reimbursed since October 2006. Through a retrospective survey in 2012, we estimated the coverage rate of the rotavirus vaccination in Flanders among infants born in 2010. Using a standardised questionnaire, 874 families were interviewed at home, collecting information on demographic characteristics, socio-economic background and documented vaccination history (updated from medical files and vaccination database, if needed). Adherence to the recommended age for vaccination (8, 12 and 16 weeks) was also assessed. The coverage rate for two doses of rotavirus vaccination was 92.2% (95% confidence interval: 90.2-93.8). Respectively 31.7% and 10.1% of the children received their first and second dose at the recommended age. Incomplete vaccination was often a deliberate choice of the parents. Only eight children (1%) were vaccinated after the maximum age of 26 weeks. Factors identified by multiple logistic regression as related to incomplete vaccination were: living in the province of Antwerp, unemployed mother, and three or more older siblings in the household. Four years after introduction, the coverage rates were surprisingly high for a vaccine that is not fully reimbursed and not readily available in the vaccinator's fridge, which is the case for the other recommended infant vaccines.

Gender-specific alterations in salivary cortisol levels in pubertal intracytoplasmic sperm injection offspring.

BACKGROUND: There is accumulating evidence that in vitro conception in humans may be associated with adverse health outcomes later in life. It has been proposed that suboptimal early life conditions may 'program' key endocrine systems. A disturbance of the hypothalamic-pituitary-adrenal (HPA) axis leading to alterations in cortisol secretion in the offspring may be such a mechanism. To date, no data on cortisol levels in children conceived by intracytoplasmic sperm injection (ICSI) are available in the literature. METHODS: In this cross-sectional study, salivary cortisol known as a key regulator of metabolism was measured and results were compared between 201 pubertal ICSI children and 196 spontaneously conceived (SC) counterparts. RESULTS: ICSI females had lower mean salivary cortisol levels (9.0 µg/l; 95% CI 8.1-9.9) than SC females (10.6 µg/l; 95% CI 9.7-11.5; p = 0.01). This difference remained after adjusting for current characteristics, early life factors and maternal characteristics. In ICSI males, no difference in cortisol levels was found in comparison with the SC group. CONCLUSION: In our study, 14-year-old female but not male ICSI teenagers were found to have lower salivary cortisol concentrations in comparison with SC peers. However, before definite conclusions can be drawn, our results should be completed by longitudinal sampling.

Personalized approach to growth hormone treatment: clinical use of growth prediction models.

The goal of growth hormone (GH) treatment in a short child is to attain a fast catch-up growth toward the target height (TH) standard deviation score (SDS), followed by a maintenance phase, a proper pubertal height gain, and an adult height close to TH. The short-term response variable of GH treatment, first-year height velocity (HV) (cm/year or change in height SDS), can either be compared with GH response charts for diagnosis, age and gender, or with predicted HV based on prediction models. Three types of prediction models have been described: the Kabi International Growth Hormone Study models, the Gothenburg models and the Cologne model. With these models, 50-80% of the variance could be explained. When used prospectively, individualized dosing reduces the variation in growth response in comparison with a fixed dose per body weight. Insulin-like growth factor-I-based dose titration also led to a decrease in the variation. It is uncertain whether adding biochemical, genetic or proteomic markers may improve the accuracy of the prediction. Prediction models may lead to a more evidence-based approach to determine the GH dose regimen and may reduce the drug costs for GH treatment. There is a need for user-friendly software programs to make prediction models easily available in the clinic.

References and cutoffs for triceps and subscapular skinfolds in Norwegian children 4-16 years of age.

BACKGROUND/OBJECTIVES: To establish new reference values for triceps (TSF) and subscapular (SSF) skinfolds of Norwegian children 4-16 years of age, and to define cutoff values for overweight and obesity using the criteria of the International Obesity Task Force (IOTF). SUBJECTS/METHODS: A cross-sectional sample of 4606 children 4-16 years of age, part of a larger growth study, was used to estimate reference curves with the LMS method; suggested cutoffs were selected using receiver operating characteristic analyses. RESULTS: Reference values for TSF and SSF are presented as percentiles. Mean skinfold size increased with age. Girls had higher values than boys over the entire age range. There was a strong positive correlation between both skinfolds and body mass index (BMI). For all ages together, a cutoff of 1.0 standard deviation score (SDS) gave a sensitivity of 76% for SSF, and 70% for TSF to detect overweight, with a corresponding specificity of 92% for both. To detect obesity, a cutoff value of 1.3 SDS gave a sensitivity of 91% and specificity of 90% for SSF. Corresponding values for TSF were 86% for the sensitivity, and 91% for the specificity. CONCLUSIONS: This study presents new reference values for TSF and SSF skinfolds in Norwegian children 4-16 years of age. Both skinfolds had a high-discriminating power to detect overweight and obesity as defined by the IOTF BMI criteria.

Blood pressure in ICSI-conceived adolescents.

STUDY QUESTION: Do young adolescents conceived by ICSI display a higher blood pressure than spontaneously conceived (SC) adolescents? SUMMARY ANSWER: In our study, 14-year-old male and female ICSI teenagers were not found to have increased blood pressure at rest. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Only limited data are available regarding the cardiovascular risk of children born after assisted conception and up till now, no data on the cardiovascular health in pubertal children conceived by ICSI have been published. In this study, resting blood pressure and blood pressure response to a psychological stressor were measured in a cohort of 14-year-old teenagers conceived by ICSI and compared the results with those of a group of SC peers. DESIGN: In this cross-sectional study, resting blood pressure measurements were available from 217 singleton ICSI children (116 boys, 101 girls) and 223 singleton control children born after spontaneous conception (115 boys, 108 girls). Continuous blood pressure measurements, performed during a psychological stress test, were available for only 67 ICSI and 38 SC children. PARTICIPANTS AND SETTING: The study group comprised adolescents conceived by ICSI predominantly because of male factor infertility and they were part of a previously published cohort followed since birth; controls were a cross-sectional sample of peers born to fertile parents and recruited from comparable schools as those attended by the ICSI teenagers. Response rates were 56% (tested/reached) in the ICSI group and 50% (agreed/eligible) in the SC group, but information regarding health could be obtained in 63 and 72% of the ICSI and SC children, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: ICSI girls had a comparable resting systolic (109 ± 9 mmHg) and diastolic (64 ± 6 mmHg) blood pressure in comparison with girls in the SC group (111 ± 9 mmHg, P = 0.2 and 66 ± 7 mmHg, P = 0.05), even after adjustment for age and height. After adjustment for current body characteristics, early life and parental background factors, systolic and diastolic blood pressure remained comparable in both groups. In ICSI boys, a slightly lower systolic (113 ± 10 mmHg), but comparable diastolic (64 ± 6 mmHg) resting blood pressure was found in comparison with the SC group (116 ± 9 mmHg; P = 0.04 and 65 ± 5 mmHg; P = 0.1). After adjustment for height and age, systolic and diastolic blood pressure were comparable in both groups (P = 0.7 and P = 0.6). After correction for current body characteristics, early life and parental factors, ICSI and SC boys still had comparable systolic (difference in ICSI versus SC: -1.1 mmHg; 95% CI: -3.8-1.6; P = 0.4) and diastolic (difference in ICSI versus SC: -1.2 mmHg; 95% CI: -3.2-0.7; P = 0.2) blood pressure measurements. In the small subsample of girls and boys with continuous blood pressure readings, the systolic and diastolic blood pressure response to the stress test was not significantly different between the ICSI and SC groups even after taking into account the baseline values. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: Despite the rather low response rate in the ICSI group and the fact that no information on current health status could be obtained from more than a quarter of the eligible comparison group, the non-participating analysis in the ICSI as well in the SC group did not reveal differences between participating and non-participating children regarding clinical characteristics. The negative results for the sub-analysis on blood pressure response to stress should be interpreted with caution, because these data were available for only a small number of children, and the analysis may be underpowered. This result can only rule out a large effect on blood pressure responsiveness to a psychological stressor. Although our sample size appears to be appropriate, our results need confirmation by others and in larger cohorts when more data become available. GENERALIZABILITY TO OTHER POPULATIONS: Our results are the first described ever in ICSI offspring, born to parents suffering from predominantly male factor infertility. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by research grants from Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Onderzoeksraad Vrije Universiteit Brussel and Wetenschappelijk Fonds Willy Gepts. Unconditional grants from MSD Belgium, Merck International, IBSA Institut Biochimique and Ferring International Center are kindly acknowledged.

Pubertal development in ICSI children.

BACKGROUND: To date, information on the pubertal development of adolescents born after ICSI is scarce, since the very first cohort is only now reaching young adulthood. In this study, pubertal development at the age of 14 was characterized in a longitudinally followed cohort of ICSI-conceived teenagers and compared with that of a spontaneously conceived (SC) control group. METHODS: Pubertal development was assessed by Tanner staging (breast, genital and pubic hair development) and age at menarche in 217 singleton ICSI-conceived children (116 boys, 101 girls) and 223 SC peers (115 boys, 108 girls). ICSI teenagers were part of a previously published cohort followed since birth; controls were a cross-sectional sample recruited from schools. Differences in pubertal development between ICSI and SC children were analyzed with logistic regression of current status data. RESULTS: Mean age at menarche was similar in ICSI and SC girls (13.1 ± 1.2 versus 13.1 ± 1.4 years; P = 0.8). Breast developmental at the age of 14 years was less advanced in ICSI females compared with SC females, even after adjustment for demographic (age, BMI), genetic (maternal age at menarche), social (maternal educational level) and early life factors (birthweight, gestational age and maternal parity) [odds ratio (OR) 0.5; 95% confidence interval (CI) 0.3-0.8]. After adjustment, genital development in the 14-year-old boys was comparable in the ICSI and SC groups (OR 1.1; 95% CI 0.7-1.8), pubic hair development was comparable in the ICSI and SC groups, for both males (OR 0.9; 95% CI 0.7-1.6) and females (OR 0.7; 95% CI 0.4-1.3). CONCLUSIONS: We found that pubertal development, characterized by menarche, genital development in males and pubic hair development in males and females, was comparable in the ICSI and SC groups. Breast developmental was less advanced in ICSI females compared with SC peers, even after adjustment for known potential confounders. In order to confirm that progression through subsequent stages of pubertal development occurs on a timely basis in ICSI teenagers, long-term follow-up studies up to adulthood are required.

Waist circumference and waist-to-height ratio in Norwegian children 4-18 years of age: reference values and cut-off levels.

AIM: To establish reference values for waist circumference and waist-to-height ratio of Norwegian children. MATERIAL: Data were collected in 2003-2006 as part of a cross-sectional study, including 5725 children 4-18 years of age. Reference curves were fitted with the LMS method; appropriate cut-offs were selected using receiver operating characteristic analysis. RESULTS: Reference values for waist circumference and waist-to-height ratio are presented. Mean waist circumference increased with age for both genders. Boys had a higher waist circumference at almost all ages. Mean waist-to-height ratio decreased until early adolescence and thereafter increased slightly towards adult age. There was a strong positive correlation between waist circumference and BMI (r = 0.907, p < 0.01) and a moderate positive correlation between waist-to-height ratio and BMI (r = 0.397 p < 0.01). A waist circumference cut-off value of 1.0 SDS (85th percentile) gave a sensitivity of 79% and a specificity of 94% to detect overweight. A cut-off value of 1.6 SDS (95th percentile) gave a sensitivity of 94% and a specificity of 96% to detect obesity. CONCLUSION: This study presents the first reference values of waist circumference and waist-to-height ratio for Norwegian children 4-18 years, which also represent the first reference in Scandinavian schoolchildren. The 85th and 95th percentiles of waist circumference are proposed as appropriate cut-offs for central overweight and obesity.