Birth Weight Standard Deviation Score Research Articles

Sensor-derived glycaemic metrics in pregnant women with type 1 diabetes randomised to faster acting insulin aspart or insulin aspart-A secondary analysis of the CopenFast trial.

We compared sensor-derived glycaemic metrics in pregnant women with type 1 diabetes (T1D) randomised to faster acting insulin aspart (faster aspart) or insulin aspart (IAsp). A pre-planned secondary analysis of the CopenFast trial included women with T1D using intermittently scanned continuous glucose monitoring (isCGM) during pregnancy. Glycaemic metrics, including time in range (TIRp, 3.5-7.8 mmol/L) and time below range in pregnancy (TBRp, <3.5 mmol/L), were evaluated in the intervals: from randomisation (median 9.5 weeks, interquartile range 9.0-11.0) to 21 weeks, from 22 to 33 weeks and from 34 to 37 weeks. In total, 113 (91%) of 124 women using isCGM in the original trial were included. At randomisation, glycaemic metrics were comparable in both groups. Women randomised to faster aspart achieved higher TIRp from 22 to 33 weeks (estimated treatment difference 5.1% [95% confidence interval 0.3; 9.7], p = 0.04) and mean TIRp >70% from randomisation to 21 weeks onwards, while this was achieved after 34 weeks in women randomised to IAsp. TBRp remained stable around 4% throughout pregnancy in both groups. One (2%) versus 5 (9%) experienced ≥1 severe hypoglycaemic event (odds ratio 0.93 [-0.2; -0.01], p = 0.04). Infant birthweight standard deviation score was lower in the faster aspart group (estimated treatment difference -0.5 [-0.9; -0.03], p = 0.04); however, this attenuated when adjusting for parity (p = 0.10). Women using faster aspart achieved more TIRp and experienced less severe hypoglycaemia compared to women using IAsp. Infant birthweight was lower and thereby more appropriate in the faster aspart group; however, this attenuated when adjusting for parity.

Associations of maternal sedentary behavior and physical activity levels in early to mid-pregnancy with infant outcomes: A cohort study.

Physical activity during pregnancy is beneficial for the woman and the fetus. However, non-objective methods are often used to measure physical activity levels during pregnancy. This study aimed to evaluate objectively measured maternal early to mid-pregnancy sedentary behavior and physical activity in relation to infant well-being. This cohort study included 1153 pregnant women and was performed at Uppsala University Hospital, Uppsala, Sweden, between 2016 and 2023. Sedentary behavior and physical activity levels were measured by accelerometers during 4-7 days in early to mid-pregnancy. Outcome measures were infant birthweight standard deviation score, small-for-gestational-age, large-for-gestational-age, preterm birth (<37 weeks' gestation), spontaneous preterm birth, iatrogenic preterm birth, Apgar <7 at 5 min of age, umbilical artery pH ≤7.05, and admission to the neonatal intensive care unit (NICU). There were no associations of sedentary behavior and physical activity levels with infant birthweight standard deviation score, small-for-gestational-age, or large-for-gestational-age. After adjustment for BMI, age, smoking, parity, maternal country of birth, and a composite of pre-pregnancy disease, the most sedentary women had higher odds of preterm birth (adjusted odds ratio (AOR) 2.47, 95% confidence interval (CI) 1.17-5.24, p = 0.018), and NICU admission (AOR 1.93, CI 1.11-3.37, p = 0.021) than the least sedentary women. The most physically active women had lower adjusted odds for NICU admission (AOR 0.45, CI 0.26-0.80, p = 0.006) than the least physically active women. Objectively measured levels of sedentary behavior and physical activity in early to mid-pregnancy were not associated with standardized infant birth size. Sedentary behavior was associated with an increased likelihood of preterm birth and NICU admission, while high level of physical activity was associated with a decreased likelihood of admission to NICU.

Centralisation of extremely preterm births and decreased early postnatal mortality in Sweden, 2004-2007 versus 2014-2016.

We evaluated the increased centralisation of extremely preterm (EPT) births in Sweden in relation to the changes in mortality and morbidity. Population-based data covering Swedish live births from 22 + 0 to 26 + 6 weeks of gestation during 2004-2007 and 2014-2016 were analysed for associations between time-period, birth within (inborn) or outside (outborn) regional centres, and outcomes. Among 1626 liveborn infants, 703 were born in 2004-2007 and 923 in 2014-2016. Birth outside (vs. within) regional centres was associated with a higher infant mortality even after adjustment for birth cohort, gestational age, birthweight standard deviation score and infant sex (adjusted odds ratio 2.01, 95% confidence interval 1.31-3.07, p = 0.001). The higher 1-yearmortality in outborn infants was mainly due to more deaths within 24 h after birth. Outborn infants had a higher incidence of intraventricular haemorrhage grade 3-4 than inborn infants (22% vs. 14% in 2004-2007, and 22% vs. 13% in 2014-2016, both p < 0.05). While survival to 1 year without major morbidity increased in inborn infants (33%-40%, p = 0.008), it remained unchanged in outborn infants (29% vs. 30%, p = 0.88). Centralisation of EPT births contributed to a lower 1-year mortality in 2014-2016 than that in 2004-2007, attributed to a decrease in deaths before 24 h among inborn infants.

Cerebral white matter hyperintensities in adults born small for gestational age at 12 years after cessation of childhood growth hormone treatment: a prospective cohort study including untreated controls

Increased cerebrovascular morbidity was reported in adults born small for gestational age (SGA) who were treated with growth hormone (GH) during childhood compared to the general population. Yet, previous studies lacked an appropriate control group which is a major limitation. We prospectively studied cerebral white matter hyperintensities (WMHs) in adults born SGA at 12 years after cessation of childhood GH-treatment (SGA-GH), compared to appropriate controls. In this prospective cohort study, performed between May 2016 and December 2020, total WMHs, periventricular WMHs (PVWMHs) and deep WMHs (DWMHs) were the primary outcomes of the study, they were qualitatively assessed using 3Tesla (T) Magnetic Resonance Imaging (MRI) and scored using the Fazekas scale in SGA-GH adults and in 3 untreated control groups: adults born SGA with persistent short stature (SGA-S), adults born SGA with spontaneous catch-up growth to a normal height (SGA-CU) and adults born appropriate for gestational age with a normal height (AGA). Regression analyses were performed in the total cohort to evaluate the associations of GH-treatment and birth characteristics with WMHs. 297 adults were investigated (91 SGA-GH, 206 controls). Prevalence of total WMHs was 53.8% (95% CI 43.1-64.3) in SGA-GH, 40.5% (95% CI 25.6-56.7) in SGA-S, 73.9% (95% CI 61.9-83.7) in SGA-CU and 41.1% (95% CI 31.1-51.6) in AGA adults. No statistically significant differences in total WMHs, PVWMHs and DWMHs were found between SGA-GH compared to SGA-S and AGA adults. Highest prevalence of all type of WMHs was found in SGA-CU adults compared to all groups. Higher prevalence of total WMHs was associated with lower birth weight standard deviation score (SDS), but not with GH-treatment. Our findings suggest that GH-treatment in children born SGA has no negative impact on the prevalence of all type of WMHs at 12 years after GH cessation compared to appropriate controls. SGA-CU adults had the highest prevalence of all type of WMHs around age 30 years. Novo Nordisk.

Combined maternal central adiposity measures in relation to infant birth size

Improvement of prenatal identification of large-for-gestational-age (LGA) infants could lower the risk for adverse outcomes. Therefore, we sought to evaluate the association of a combination of maternal waist circumference (WC) and abdominal fat depths with infant birth size. A cohort study including 1240 women was performed between 2015 and 2018 at Uppsala University Hospital, Sweden. Maternal WC was measured at the first antenatal visit, and visceral (VF) and subcutaneous (SCF) fat depths by ultrasound at the second-trimester anomaly scan. Waist circumference, VF, and SCF were categorized as low or high (cut-offs WC ≥ 88 cm, VF ≥ 54 mm, SCF ≥ 21 mm). Outcomes were birth weight standard deviation score (BWSDS) and LGA (BWSDS > 90th and > 97th percentile). Secondary outcome was small-for-gestational-age (SGA, BWSDS < 10th and < 3rd percentile). Univariate analysis of variance and logistic regression analyses were performed adjusted for maternal weight, height, parity, smoking, country of birth, pregestational diabetes, and chronic hypertension. For both high and low WC, high VF was positively associated with BWSDS and LGA. There was no association with SGA. The results did not demonstrate any value of the combination of WC and fat depth measures in predicting infant birth size but suggested VF as a marker for large infants.

Endocrine and metabolic disorders in adolescent and adult patients born small for gestational age.

Children born small for gestational age (SGA), defined by a birth weight and/or length standard deviation score (SDS) of < -2 based on an appropriate reference population, represent a diverse group due to multiple underlying causes of reduced growth. This classification results in a heterogeneous patient cohort. SGA children are prone to endocrinological and metabolic issues not only in childhood but also extending into adolescence and adulthood. This population faces elevated health risks, including persistent short stature, premature adrenarche, pubertal development alterations, neurocognitive problems, and metabolic syndrome. Insulin resistance emerges as a pivotal factor c nht6j7ikontributing to these metabolic complications, prominently featuring obesity, insulin resistance, hypertension, and an increased risk of type 2 diabetes mellitus in adulthood. These medium- to long-term complications significantly impact their quality of life. Growth hormone (GH) therapy for short children born SGA facilitates height normalization throughout childhood, adolescence, and into adulthood. Catch-up growth, however, correlates with heightened risks of obesity, insulin resistance, and metabolic syndrome. Conversely, those without catch-up growth tend to exhibit pronounced short stature and cognitive dysfunction. Given these determinants, comprehensive management and clinical monitoring of SGA children should commence in the neonatal period and extend into adulthood. Recognizing and addressing these challenges early in life can mitigate the long-term impact on health and well-being, emphasizing the importance of a lifelong approach to their care.

Maternal early mid-pregnancy adiponectin in relation to infant birth weight and the likelihood of being born large-for-gestational-age

This study aimed to evaluate the association of maternal adiponectin with infant birth size in 1349 pregnant women at Uppsala University Hospital, Sweden. The mean age of the women was 31.0 years, and 40.9% were nulliparous. Maternal early mid-pregnancy adiponectin was measured in microgram/mL. Linear regression models were performed to evaluate the association between adiponectin and infant birth weight. Logistic regression models were used to evaluate adiponectin in relation to the odds of giving birth to an infant large-for-gestational-age (LGA, infant birth weight standard deviation score > 90th percentile). Adjustments were made for early pregnancy BMI and diabetes mellitus. Prior adjustments, adiponectin was inversely associated with infant birth weight (β − 17.1, 95% confidence interval (CI) − 26.8 to − 7.4 g, P < 0.001), and one microgram/mL increase in adiponectin was associated with a 9% decrease in the odds of giving birth to an LGA infant (odds ratio 0.91, CI 0.85–0.97, P = 0.006). The associations did not withstand in the adjusted models. We found a significant interaction between adiponectin and infant sex on birth size. This interaction was driven by an inverse association between maternal adiponectin and birth size in female infants, whereas no such association was found in males.

Clinical factors associated with birth weight of infants born to pregnant women with diabetes.

We aimed to examine the clinical factors associated with the birth weight of infants born to Japanese pregnant women with diabetes. This retrospective observational study enrolled 204 Japanese women with singleton pregnancies with type 1 diabetes (n = 135) or type 2 diabetes (n = 69). We used multiple regression analyses to examine factors associated with birth weight standard deviation (SD) scores. In addition, we compared the clinical findings among the groups of mothers who gave birth to appropriate for gestational age infants (AGA group), large for gestational age infants (LGA group), and small for gestational age infants (SGA group). Multiple regression analyses showed that the birth weight SD score was positively associated with type 2 diabetes. In women with type 1 diabetes, the birth weight SD score was positively associated with glycated albumin levels and gestational weight gain and negatively associated with pre-pregnancy underweight. Only gestational weight gain was positively associated with birth weight SD scores in women with type 2 diabetes. Glycated hemoglobin levels, gestational weight gain, and triglyceride levels were significantly higher in the LGA group than in the AGA group. The SGA group showed significantly lower gestational weight gain and triglyceride levels than the AGA group. These results suggest that it is important to manage not only blood glucose levels but also pre-pregnancy body weight and gestational weight gain for appropriate fetal growth. The effects of clinical factors on infant birth weight may differ between patients with type 1 and those with type 2 diabetes.

Extremely and very preterm children who were born appropriate for gestational age show no differences in cortisol concentrations or diurnal rhythms compared to full-term children.

The objective of this study was to compare the diurnal variations in cortisol and cortisone concentrations in serum and saliva among extremely preterm (EPT), very preterm (VPT), and full-term (FT) children, all born appropriate for gestational age (AGA). EPT, VPT, and FT children, all born AGA, were recruited from two healthcare centers. Cortisol and cortisone concentrations in serum and saliva were measured by liquid chromatography-mass spectrometry (LC‒MS). Statistical analysis was performed using nonparametric tests. A total of 101 children (5.0-8.9 years old) were included in this study: EPT=18, VPT=43 and FT=40. All groups had similar distributions in terms of age, birth weight standard deviation score (SDS) and BMI (SDS), showing no differences in serum ACTH, cortisol, or cortisone levels. Additionally, salivary cortisol and cortisone concentrations decreased significantly throughout the day (p values<0.0001). Salivary cortisol concentrations were below the limit of detection (0.55 nmol/L) before dinner andbefore bedtime in approximately one-third and two-thirds of all children, respectively. Salivary cortisone was detectable in all but one sample. The diurnal cortisol rhythm was preserved in all preterm children, regardless of their gestational age, and no differences in cortisol concentrations among the groups were found. This may have significant implications for the clinical management and follow-up of preterm individuals.

176-OR: CopenFast Trial—Fetal Growth and Glycemic Control in Pregnant Women with Type 1 or Type 2 Diabetes Using Faster-Acting Insulin Aspart or Insulin Aspart—A Randomized Controlled Trial

Aim: To evaluate the effect of faster-acting insulin aspart (faster aspart) vs. insulin aspart (IAsp) on fetal growth and glycemic control in pregnant women with type 1 or type 2 diabetes. Methods: In a single-center, open-label trial from November 2019 to May 2022 women were stratified by diabetes type and insulin treatment modality (multiple daily injections or insulin pump) and randomized to faster aspart or IAsp from 8 to 13 weeks. Primary outcome was offspring birthweight standard deviation (SD) score. Secondary outcomes included mild hypoglycemia (managed by the woman) in the previous week, HbA1c at inclusion, 21, 33, and 35 weeks, and severe hypoglycemia (requiring third party assistance) reported in a structured interview. Results: In total, 216 women were included and randomized to faster aspart or IAsp (n=109 vs. n=107). Baseline data were comparable in both groups. Primary outcome data were available in 94% (71% type 1 (of which 19% on insulin pump), 29% type 2 diabetes). Offspring birthweight SD score was median 0.7 (interquartile range -0.3-2.0) vs. 1.1 (0.4-1.9), mean difference -0.2 (95% confidence interval -0.6-0.1), p=0.23 with 41% vs. 46% large for gestational age infants (p=0.39). From randomization to delivery 1 (1%) vs. 7 (7%) women reported severe hypoglycemia (p=0.07) with fewer events reported by women using faster aspart compared to IAsp (1 vs. 10 events, p=0.03). At 33 weeks, women using faster aspart reported fewer mild hypoglycemic events in the previous week compared to IAsp (2.0 (0.8 - 4.0) vs. 3.0 (1.0 - 5.0), p=0.03), while HbA1c was 41 (38-46) vs. 43 (39-46) mmol/mol, p=0.28. Prevalence of preeclampsia was 15% vs. 12% (p=0.51) and preterm delivery &amp;lt;37 weeks 19% vs. 22% (p=0.64). No perinatal deaths were reported. Conclusion: In pregnant women with type 1 or type 2 diabetes, use of faster aspart resulted in comparable fetal growth and HbA1c with less severe hypoglycemia compared to IAsp. Disclosure S.K.Noergaard: Research Support; Novo Nordisk A/S. E.R.Mathiesen: Advisory Panel; Novo Nordisk, Research Support; Novo Nordisk, Speaker's Bureau; Novo Nordisk. K.Nørgaard: Advisory Panel; Medtronic, Novo Nordisk, Research Support; Medtronic, Dexcom, Inc., Novo Nordisk, Zealand Pharma A/S, Speaker's Bureau; Medtronic, Novo Nordisk, Stock/Shareholder; Novo Nordisk. T.D.Clausen: None. J.Søholm: Research Support; Novo Nordisk A/S. P.Holmager: None. N.C.Do: Research Support; Novo Nordisk Foundation. P.Damm: Other Relationship; Novo Nordisk A/S. L.Ringholm: Research Support; Novo Nordisk A/S. Funding Novo Nordisk A/S (U1111-1209-6358)

Deciphering Epigenetic Backgrounds in a Korean Cohort with Beckwith-Wiedemann Syndrome.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder caused by genetic or epigenetic alterations at two imprinting centers (ICs) in the 11p15.5 region. Delineation of the molecular defects is important for prognosis and predicting familial recurrence. We evaluated epigenetic alterations and potential epigenotype-phenotype correlations in Korean children with BWS. Forty children with BWS with proven genetic or epigenetic defects in the 11p15.5 region were included. The phenotype was scored using the BWS consensus scoring system. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), bisulfite pyrosequencing, a single-nucleotide polymorphism microarray, and CDKN1C sequencing were used for confirmative diagnosis. Patients met the criteria for genetic testing, with a mean clinical score of 5.4±2.0. Methylation alterations were consistent between MS-MLPA and bisulfite pyrosequencing in all patients. Twenty-six patients (65.0%) had IC2 loss of methylation (IC2-LoM), 11 (27.5%) had paternal uniparental disomy (patUPD), and one (2.5%) had IC1 gain of methylation. Macroglossia and external ear anomalies were more common in IC2-LoM than in patUPD, and lateralized overgrowth was more common in patUPD than in IC2-LoM (all P<0.05). Methylation levels at IC2 were inversely correlated with birth weight standard deviation score (r=-0.476, P=0.014) and clinical score (r=-0.520, P=0.006) in the IC2-LoM group. Comprehensive molecular analysis of the 11p15.5 region revealed epigenotype-phenotype correlations in our BWS cohort. Bisulfite pyrosequencing can help clarify epigenotypes. Methylation levels were correlated with fetal growth and clinical severity in patients with BWS.

Association of Plasma Cortisol Levels with Gestational Age and Anthropometric Values at Birth in Preterm Infants.

There are no study reports to clarify the association between gestational age (GA) or anthropometric values at birth, and plasma cortisol levels in the blood of preterm infants at birth and at one month of age. This hospital-based retrospective cohort study included infants born at <37 weeks’ gestation between 2019 and 2021. First, the association between plasma cortisol level and GA or anthropometric values at birth (birth weight standard deviation score [SDS], birth length SDS, and birth head circumference SDS) was identified by regression and multiple regression analyses. Second, plasma cortisol levels in the umbilical cord at birth and at one month of age were compared between small-for-gestational age (SGA) and non-SGA infants. Sixty-one preterm infants were enrolled (SGA: 24 and non-SGA: 37). Plasma cortisol levels at birth were significantly associated with GA. Plasma cortisol levels at one month of age were associated with GA and birth head circumference SDS. Plasma cortisol levels at birth were significantly higher in SGA than non-SGA (p = 0.010). GA was an independent determinant of plasma cortisol levels at birth. SGA infants had a high plasma cortisol level at birth; resulting in speculation that a high plasma cortisol level at birth may predict abnormal neurological outcomes.

O-086 Assisted reproductive technology does not influence body mass index (BMI) in a cohort of 606 children aged 6-9 years

Abstract Study question Is BMI in children conceived after frozen embryo transfer different from children conceived after fresh embryo transfer and after natural conception? Summary answer BMI in children conceived after frozen embryo transfer was similar to BMI in children conceived after fresh embryo transfer or children born after natural conception. What is known already Children conceived after frozen embryo transfer (FET) have higher risk of being born large for gestational age (LGA) than children conceived after natural conception (NC). Generally, being born LGA increases the risk of obesity in childhood. Childhood BMI is strongly associated with obesity and cardiometabolic disease and mortality in adulthood. The long-term effects of ART on the metabolic health of the offspring and the underlying mechanisms are scarcely explored. However, it has been proposed that ART may induce epigenetic variations around fertilization, implantation, and early embryonic stages that may influence size at birth. Study design, size, duration The study “Health in Childhood following Assisted Reproductive Technology” (HiCART) includes 606 singletons (292 boys, 314 girls) – 200 conceived after FET; 203 after fresh-ET; and a random sample of 203 naturally conceived children matched for age and sex. All children were born in Eastern Denmark from 2009-2013 and had a clinical examination performed at the Copenhagen University Hospital - Rigshospitalet when they were 6-9 years of age. Participants/materials, setting, methods The children underwent a clinical examination with anthropometric measurements, whole-body dual-energy x-ray absorptiometry-scan (DXA), pubertal staging, and a blood sample. All anthropometric measurements were converted to standard deviation scores (SDS) using a Danish reference. Parents filled in a questionnaire regarding the pregnancy and the current health of the child and themselves. Maternal, obstetric and neonatal data from the national ART and birth registry were obtained. Main results and the role of chance Children conceived after FET had higher birthweight SDS (0.20SDS, 1.09SD) than children conceived after fresh-ET (-0.22SDS, 1.00SD), p &amp;lt; 0.001 and children conceived naturally (-0.16SDS, 1.09SD), p = 0.001. Mothers conceiving naturally were younger and had higher parity than mothers conceiving after ART. The three groups were similar regarding pregestational maternal BMI and gestational age. Puberty had started in 57 children (54 girls), evenly distributed among the groups. There were no differences in height SDS between FET (0.25SDS, 1.00SD) compared to fresh-ET (0.17SDS, 0.96SD), p = 0.50 and compared to NC (0.07 SDS, 1.06SD), p = 0.11 or in weight SDS between FET (0.22SDS, 1.07SD) compared to fresh-ET (0.10 SDS, 1.06SD), p = 0.22 and compared to NC (0.14SDS, 1.00SD), p = 0.43. Similarly, no differences were found in BMI SDS between FET (0.16SDS, 1.16SD) compared to fresh-ET (0.04SDS, 1.10SD), p = 0.25 and compared to NC (0.20SDS, 1.01SD), p = 0.80. Our primary endpoint BMI SDS remained non-significant after adjustment for child sex, age and birthweight SDS, parity, maternal BMI and smoking in pregnancy. Limitations, reasons for caution The sample size was decided to be able to detect a difference of 0.3 SDS in childhood BMI, corresponding to a 3.4% increased mortality hazard. Thus, smaller differences in BMI SDS may be overlooked. As the participation rate was between 18-42% in the three groups, selection bias cannot be excluded. Wider implications of the findings The increased birth weight in children conceived after FET did not translate into a difference in BMI in this large cohort. Since BMI in childhood is a strong biomarker of cardiometabolic disease later in life, the findings are reassuring and may reduce concerns associated with the long-term consequences of FET. Trial registration number NCT03719703

Percentile-Based Reference Values of Umbilical Cord Blood Insulin-like Growth Factor 1 in Japanese Newborns.

We aimed to create percentile-based reference values of the umbilical cord blood insulin-like growth factor-1 (IGF-1) levels in Japanese newborns, as these values have not yet been established. A total of 259 newborns were classified into four gestational-age-at-birth (GA) groups: extremely preterm (<28 weeks); early preterm (28–33 weeks); late preterm (34–36 weeks); and term (≥37 weeks). They were further subclassified as small-for-gestational-age (SGA) or non-SGA. The 10th, 25th, 50th, 75th, and 90th percentiles of the umbilical cord blood IGF-1 levels were calculated and compared between the groups by using reference values of 9, 18, 33, 52, and 71 ng/mL, respectively. In the extremely preterm group, the IGF-1 levels were significantly lower than those in the early preterm, late preterm, and term groups (13.5, 24.0, 44.5, and 47.5 ng/mL, respectively; p < 0.001). The umbilical cord blood IGF-1 levels in the SGA newborns were significantly lower than those in the non-SGA newborns in all subgroups. In multivariate analyses, the GA and birth weight standard deviation scores were independent determinant factors for the umbilical cord blood IGF-1 levels. Thus, we established percentile-based reference values of umbilical cord blood IGF-1 in Japanese newborns; these reference values can be applied on the basis of the extent of prematurity and the SGA status.

Abstract 2: Effectiveness and safety of early growth hormone treatment in children born small for gestational age: Long-term data from NordiNet® International Outcome Study (IOS) and ANSWER program

Background: Growth hormone (GH) is indicated for the treatment of short stature in children born small for gestational age (SGA) who fail to show catch-up growth. In pilot studies, early initiation of GH has been associated with favorable growth responses in short SGA children. However, few studies have examined the short- and long-term effects of initiating GH in children born SGA who are <4 years (yr) of age, compared with those starting later. This analysis therefore investigated the effect of age at GH initiation on long-term effectiveness and safety in children born SGA.Methods: The NordiNet IOS (NCT00960128) and ANSWER (NCT01009905) programs are complementary, noninterventional, multicenter studies that evaluated the long-term effectiveness and safety of Norditropin (somatropin; Novo Nordisk A/S, Denmark) as prescribed in real-life clinical practice. In this analysis, children born SGA who were prepubertal at GH initiation were grouped according to age at GH start: <4 yr, 4-6 yr, and ≥6 yr. Patient characteristics at birth and at GH start, auxological measurements, and adverse events were evaluated in each group.Results: Overall, 3351 SGA patients were included in the effectiveness set (age at GH start: <4 yr [n=389, 54.8% male]; 4-6 yr [n=1048, 57.6% male]; and ≥6 yr [n=1914, 56.6% male]). The proportion of patients born pre-term (<37-week gestation) was 38.6% in the <4 yr group, 36.1% in the 4-6 yr group, and 28.2% in the ≥6 yr group. Mean (SD) birth length standard deviation score (SDS) and birth weight SDS were: −2.9 (1.6) and −2.3 (1.2) in the <4 yr group, −2.8 (1.3) and −2.2 (1.1) in the 4-6 yr group, and −2.5 (1.4) and −2.0 (1.2) in the ≥6 yr group. Mean (SD) age at GH start was 3.1 (0.7), 4.9 (0.6), and 9.3 (2.2) years in the <4 yr, 4-6 yr, and ≥6 yr groups, respectively. Mean (SD) GH duration and daily GH dose in the study were: 3.5 (3.1) yr and 0.044 (0.016) mg/kg in the <4 yr group, 4.1 (3.1) yr and0.039 (0.012) mg/kg in the 4-6 yr group, and 3.5 (2.5) yr and 0.042 (0.012) mg/kg in the ≥6 yr group. Mean (SD) height SDS (HSDS) at GH start was −3.3 (1.2) in the <4 yr group, −3.1 (0.9) in the 4-6 yr group, and −2.8 (0.8) in the ≥6 yr group. After 4 and 8 yr of GH, mean (SD) ÄHSDS from baseline was 1.7 (0.7) and 2.5 (0.6) in the <4 yr group, 1.6 (0.7) and 2.2 (0.8) in the 4-6 yr group and 1.3 (0.7), and 1.7 (0.6) in the ≥6 yr group. Among patients who reached near-adult height in the study, mean (SD) HSDS was −1.9 (0.6) in the <4 yr group (n=3), −1.9 (0.8) in the 4-6 yr group (n=10), and −1.8 (1.0) in the ≥6 yr group (n=220). In the safety set (n=5643), the most commonly reported non-serious adverse reactions (AR) were headache (n=20) and arthralgia (n=5). The most common serious ARs were headache (n=3) and epiphysiolysis (n=4). ARs and serious ARs were distributed equally among groups.Conclusions: This analysis of real-world data confirms the effectiveness and safety of GH in children born SGA, irrespective of patient age at treatment initiation.

Preschool-children's height, trend, and causes: Japanese national surveys 1990-2010.

.We observed trends in the height of children aged 3 to 6 in Japan using data from the National Growth Survey on Preschool Children in the years 1990, 2000, and 2010. Average standard deviation (SD) scores of height decreased from 0.39 (SD 1.02) in 1990 (n = 3,684) to 0.37 (SD 1.05) in 2000 (n = 2,981) and 0.33 (SD 1.07) in 2010 (n = 2,027). Mothers of children in later waves were taller, older, and more likely to be primiparous; children in later waves had shorter gestational age, lower birth weight, and were less likely to have been fed less with formula or solid foods before 6 mo. The only factor that consistently contributed to a reduction in children’s height for both 1990–2000 and 2000–2010 was a reduction in birthweight SD score (indirect effect on height –1.5 [95% CI: –1.9, –1.1] mm for 1990–2000 and –1.2 [95% CI: –1.8, –0.8] mm for 2000–2010). Factors that contributed, although not significantly or consistently between the two periods, were changes in pre-pregnancy BMI, smoking during pregnancy, multiple pregnancies, gestational age, BMI at birth, and use of formula and solid foods before 6 mo. Secular increases in maternal age, height, and primiparity contributed to increasing children’s height.

Extent of absent end-diastolic flow in umbilical artery andoutcome of pregnancy.

To investigate if the extent of absent end-diastolic flow (AEDF) on umbilical artery (UA) Doppler velocimetry predicts pregnancy outcome. This was a retrospective observational study based on data from 25 000 Doppler examinations of UA flow performed between 1998 and 2017 at the Blood Flow Laboratory, Level III Perinatal Center, Lund, Sweden. All pregnancies with AEDF in the UA were identified, and the duration of AEDF as a proportion of the total duration of the cardiac cycle (Ta /Ttot ratio) was measured in digital images of the Doppler spectrum recorded at the last examination showing AEDF before delivery. Clinical data on pregnancies and neonatal outcomes were extracted from the regional perinatal database and the hospital patient records. The predictive performance of the Ta /Ttot ratio for intrauterine death and any (intrauterine or postnatal) death was assessed. A total of 170 fetuses (122 (72%) singletons and 48 (28%) twins) were included in the study. Median gestational age at birth was 189.5 days (range, 163-279 days) (i.e. 27 + 0 weeks (range, 23 + 2 to 39 + 6 weeks)), birth weight was 650 g (range, 320-3326 g) and deviation from expected birth weight (standard deviation score) was -2.975 (range, -6.38 to 0.69). There were 15 (9%) intrauterine and 26 (15%) postnatal deaths. The principal outcome variables and their relationship with Doppler velocimetry results did not differ significantly between singletons and twins, giving a rationale for using the Ta /Ttot ratio in the total study group. Mean Ta /Ttot ratio was 0.42 ± 0.08 and 0.34 ± 0.08 in stillborn and liveborn fetuses, respectively (P = 0.002). For fetuses examined before 30 weeks' gestation, a Ta /Ttot ratio cut-off of 0.30 predicted intrauterine death with 92% sensitivity and a negative predictive value (NPV) of 98% (area under receiver-operating-characteristics curve (AUC), 0.74) and predicted any death with 83% sensitivity and a NPV of 85% (AUC, 0.66). In fetuses with AEDF in the UA, duration of absent flow for at least 30% of the total cardiac cycle length might predict the risk of fetal demise, even when assessed before 30 weeks' gestation. This finding is particularly relevant to growth-restricted fetuses. After evaluation in further studies, the extent of AEDF might facilitate obstetric decision-making in very preterm growth-restricted fetuses. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal investment, life-history trajectory of the off-spring and cardiovascular disease risk in Emirati females in the United Arab Emirates

BackgroundVariations in cardiovascular disease risk (CVD) are suggested to be partly influenced by factors that affect prenatal growth patterns and outcomes, namely degree of maternal investment (proxied by birth weight and gestational age). Using the life history trajectory model, this study investigates whether maternal investment in early prenatal life associates with menarcheal age and whether maternal investment affects CVD risk in adulthood and predicts adult size and adiposity levels.MethodsA cross-sectional study was conducted among 94 healthy Emirati females. Birth weight, gestational age and menarcheal age were obtained. Anthropometrical measurements, body composition analysis, and blood pressure values were collected. Regression analyses were conducted to establish associations.ResultsThere was no association between birth weight standard deviation score (SDS) and age at menarche. When investigating the associations of birth weight SDS and age at menarche with growth indices, it was found that only birth weight was positively and significantly associated with both height (β = 1.342 cm, 95% CI (0.12, 2.57), p = 0.032) and leg length (β = 0.968 cm, 95% CI (0.08, 1.86), p = 0.034). Menarcheal age was significantly and inversely associated with fat mass index (FMI) (β = − 0.080 cm, 95% CI (− 0.13, − 0.03), p = 0.002), but not with waist circumference and fat free mass index (FFMI) (p > 0.05). Birth weight SDS was positively and significantly associated with waist circumference (β = 0.035 cm, 95% CI (0.01, 0.06), p = 0.009), FMI (β = 0.087 cm, 95% CI (0.01, 0.16), p = 0.027), and FFMI (β = 0.485 cm, 95% CI (0.17, 0.80), p = 0.003). Birth weight SDS was not significantly associated with either systolic blood pressure (SBP) or diastolic blood pressure (DBP) (p > 0.05). However, FMI, waist circumference, and FFMI were positively and significantly associated with SBP. Regarding DBP, the relationship was negatively and significantly associated with only FFMI (β = − 1.6111 kg/m2, 95% CI (− 2.63, − 0.60), p = 0.002).ConclusionAlthough the results do not fully support that Emirati females fast-life history is associated with increased chronic disease risk, the data does suggest a link between restricted fetal growth in response to low maternal investment and metabolic and reproductive health.

Normal Gestational Weight Gain Protects From Large-for-Gestational-Age Birth Among Women With Obesity and Gestational Diabetes.

Background: Pre-pregnancy obesity, excess gestational weight gain (GWG), and gestational diabetes (GDM) increase fetal growth. Our aim was to assess whether normal GWG is associated with lower risk for a large-for-gestational-age (LGA; over the 90th percentile of birth weight for sex and gestational age) infant and lower birth weight standard deviation (SD) score in the presence of GDM and maternal obesity.Methods: This multicenter case-control study is part of the Finnish Gestational Diabetes (FinnGeDi) Study and includes singleton pregnancies of 1,055 women with GDM and 1,032 non-diabetic controls. Women were divided into 12 subgroups according to their GDM status, pre-pregnancy body mass index (BMI; kg/m2), and GWG. Non-diabetic women with normal BMI and normal GWG (according to Institute of Medicine recommendations) served as a reference group.Results: The prevalence of LGA birth was 12.2% among women with GDM and 6.2% among non-diabetic women (p < 0.001). Among all women, normal GWG was associated with lower odds of LGA [odds ratio (OR) 0.57, 95% CI: 0.41–0.78]. Among women with both obesity and GDM, the odds for giving birth to a LGA infant was 2.25-fold (95% CI: 1.04–4.85) among those with normal GWG and 7.63-fold (95% CI: 4.25–13.7) among those with excess GWG compared with the reference group. Compared with excess GWG, normal GWG was associated with 0.71 SD (95% CI: 0.47–0.97) lower birth weight SD score among women with GDM and obesity. Newborns of normal weight women with GDM and normal GWG had 0.28 SD (95% CI: 0.05–0.51) lower birth weight SD scores compared with their counterparts with excess GWG. In addition, in the group of normal weight non-diabetic women, normal GWG was associated with 0.46 SD (95% CI: 0.30–0.61) lower birth weight SD scores compared with excess GWG.Conclusion: GDM, obesity, and excess GWG are associated with higher risk for LGA infants. Interventions aiming at normal GWG have the potential to lower LGA rate and birth weight SD scores even when GDM and obesity are present.

Effectiveness and Safety of Early Growth Hormone Treatment in Children Born Small for Gestational Age: Long-Term Data From NordiNet® International Outcome Study (IOS) and ANSWER Program

Background: Growth hormone (GH) is indicated for the treatment of short stature in children born small for gestational age (SGA) who fail to show catch-up growth. In pilot studies, early initiation of GH has been associated with favorable growth responses in short SGA children. However, few studies have examined the short- and long-term effects of initiating GH in children born SGA who are <4 years (yr) of age, compared with those starting later. This analysis therefore investigated the effect of age at GH initiation on long-term effectiveness and safety in children born SGA. Methods: The NordiNet IOS (NCT00960128) and ANSWER (NCT01009905) programs are complementary, non-interventional, multicenter studies that evaluated the long-term effectiveness and safety of Norditropin (somatropin; Novo Nordisk A/S, Denmark) as prescribed in real-life clinical practice. In this analysis, children born SGA who were prepubertal at GH initiation were grouped according to age at GH start: <4 yr, 4-6 yr, and ≥6 yr. Patient characteristics at birth and at GH start, auxological measurements, and adverse events were evaluated in each group. Results: Overall, 3351 SGA patients were included in the effectiveness set (age at GH start: <4 yr [n=389, 54.8% male]; 4-6 yr [n=1048, 57.6% male]; and ≥6 yr [n=1914, 56.6% male]). The proportion of patients born pre-term (<37-week gestation) was 38.6% in the <4 yr group, 36.1% in the 4-6 yr group, and 28.2% in the ≥6 yr group. Mean (SD) birth length standard deviation score (SDS) and birth weight SDS were: −2.9 (1.6) and −2.3 (1.2) in the <4 yr group, −2.8 (1.3) and −2.2 (1.1) in the 4-6 yr group, and −2.5 (1.4) and −2.0 (1.2) in the ≥6 yr group. Mean (SD) age at GH start was 3.1 (0.7), 4.9 (0.6), and 9.3 (2.2) years in the <4 yr, 4-6 yr, and ≥6 yr groups, respectively. Mean (SD) GH duration and daily GH dose in the study were: 3.5 (3.1) yr and 0.044 (0.016) mg/kg in the <4 yr group, 4.1 (3.1) yr and 0.039 (0.012) mg/kg in the 4-6 yr group, and 3.5 (2.5) yr and 0.042 (0.012) mg/kg in the ≥6 yr group. Mean (SD) height SDS (HSDS) at GH start was −3.3 (1.2) in the <4 yr group, −3.1 (0.9) in the 4-6 yr group, and −2.8 (0.8) in the ≥6 yr group. After 4 and 8 yr of GH, mean (SD) ΔHSDS from baseline was 1.7 (0.7) and 2.5 (0.6) in the <4 yr group, 1.6 (0.7) and 2.2 (0.8) in the 4-6 yr group and 1.3 (0.7), and 1.7 (0.6) in the ≥6 yr group. Among patients who reached near-adult height in the study, mean (SD) HSDS was −1.9 (0.6) in the <4 yr group (n=3), −1.9 (0.8) in the 4-6 yr group (n=10), and −1.8 (1.0) in the ≥6 yr group (n=220). In the safety set (n=5643), the most commonly reported non-serious adverse reactions (AR) were headache (n=20) and arthralgia (n=5). The most common serious ARs were headache (n=3) and epiphysiolysis (n=4). ARs and serious ARs were distributed equally among groups. Conclusions: This analysis of real-world data confirms the effectiveness and safety of GH in children born SGA, irrespective of patient age at treatment initiation.