Birth Weight SD Score Research Articles

Danish Diabetes Birth Registry 2: a study protocol of a national prospective cohort study to monitor outcomes of pregnancies of women with pre-existing diabetes

IntroductionDespite technological developments and intensified care, pregnancies in women with pre-existing diabetes are still considered high-risk pregnancies. The rate of adverse outcomes in pregnancies affected by diabetes in Denmark is...

Faster-acting insulin aspart versus insulin aspart in the treatment of type 1 or type 2 diabetes during pregnancy and post-delivery (CopenFast): an open-label, single-centre, randomised controlled trial

Faster-acting insulin aspart (faster aspart) is considered safe for use during pregnancy and breastfeeding but has not been evaluated in this population. We aimed to evaluate the effect of faster aspart versus insulin aspart on fetal growth, in women with type 1 or type 2 diabetes during pregnancy and post-delivery. This open-label, single-centre, superiority trial was conducted at Rigshospitalet, Copenhagen, Denmark. Participants aged 18 years or older with type 1 or type 2 diabetes were stratified by diabetes type and insulin treatment modality (multiple daily injections or insulin pump), randomly assigned 1:1 to faster aspart or insulin aspart, from 8 weeks and 0 days (8+0) of gestation to 13+6 weeks of gestation, and followed up until 3 months post-delivery. Primary outcome was infant birthweight SD score. Secondary outcomes included HbA1c as well as maternal and fetal outcomes in all participants during the trial. This trial is registered with ClinicalTrials.gov, NCT03770767. Between Nov 11, 2019 and May 10, 2022, 109 participants were included in the faster aspart group and 107 in the insulin aspart group. Primary outcome data were available in 203 (94%) of 216 participants, and no participants discontinued treatment during the trial. Mean birthweight SD score was 1·0 (SD 1·4) in the faster aspart group versus 1·2 (1·3) in the insulin aspart group; estimated treatment difference -0·22 [-0·58 to 0·14]; p=0·23. At 33 weeks of gestation, mean HbA1c was 42 mmol/mol (SD 6 mmol/mol; 6·0% [SD 0·9%]) versus 43 mmol/mol (SD 7 mmol/mol; 6·1% [SD 1·2%]); estimated treatment difference -1·01 (-2·86 to 0·83), p=0·28. No additional safety issues were observed with faster aspart compared with insulin aspart. Treatment with faster aspart resulted in similar fetal growth and HbA1c, relative to insulin aspart, in women with type 1 or type 2 diabetes. Faster aspart can be used in women with type 1 or type 2 diabetes during pregnancy and post-delivery with no additional safety issues. Novo Nordisk. For the Danish translation of the abstract see Supplementary Materials section.

1305-P: The Effect of Limited Pregnancy Weight Gain on Fetal Growth during Dietary Therapy in Gestational Diabetes Mellitus–Affected Women

Aims: We aimed to evaluate how diet-related maternal weight gain (GWG) affected foetal growth in gestational diabetes (GDM)-complicated pregnancies. Methods: This study involved 182 women who were sequentially diagnosed with GDM before 34 weeks of pregnancy and gave birth to live singletons at our hospital. To gauge compliance with an energy-limited “diabetic diet,” the women were divided into three groups based on their restricted (53%), appropriate (16%), and excessive (31%) weekly GWG. If necessary, insulin therapy was started in accordance with regional clinical recommendations. Results: At the time of the diagnosis of GDM at 276 ± 51 weeks, the three groups' glucose tolerance, HbA1c, weekly GWG before dietary treatment, and SD score for foetal abdominal circumference were comparable. The women were monitored for 100 ± 51 weeks, during which time 54% of them got further insulin medication, and the average GWG during dietary therapy varied amongst the three groups, weighing 0 kg, 3 kg, and 5 kg. Increased HbA1c between the time of GDM diagnosis and late pregnancy was associated with excessive weekly GWG during dietary treatment, reflecting poor dietary adherence, and newborns had a birthweight-SD score of 0.59 ± 1.6. Conclusions: In women with GDM, restricted GWG during nutritional therapy was linked to improved foetal growth. Clinical determinants of infant birthweight-SD score that are possibly modifiable include GWG during nutritional therapy and late-pregnancy HbA1c. Disclosure N.Kumar: None. S.C.Jha: None.

Impact of embryo vitrification on children’s health, including growth up to two years of age, in comparison with results following a fresh embryo transfer

To assess health outcomes, including growth up to 2 years of age, in children born after embryo vitrification in comparison with children born after fresh embryo transfer. A prospective cohort study. A single-center university hospital. Singletons born after the transfer of vitrified or fresh embryos, either at the cleavage or blastocyst stage between 2014 and 2018, were included. Multiple linear and logistic regression analyses were used to study the association between outcomes after vitrified versus fresh embryo transfer, controlling for neonatal, treatment, and maternal characteristics. Subgroup analysis according to cycle protocol (hormone replacement vs. natural cycle) and strategy (freeze-all vs. previous fresh cycle) was also performed. Measurements at birth and growth in infancy and childhood, as well as health outcomes, including congenital malformations, interventions, medication use, and hospitalizations are reported. Birth characteristics were available for 1237 and 2063 children born after embryo vitrification and fresh embryo transfer, respectively. Follow-up data were available for 582 and 757 children at infancy and for 233 and 296 children at 2 years, respectively. Birthweight, height, and head circumference SD scores of children born after embryo vitrification were higher than children born after fresh embryo transfer, even after adjustment for neonatal, treatment, and maternal characteristics. In infancy, weight and height SD scores were larger for children born after embryo vitrification, but not after adjustment for covariates. In childhood, no differences in anthropometry were observed between the groups. Weight and height gain from birth to infancy and from infancy to early childhood were comparable between the groups. Comparable rates of severe developmental problems, hospital admissions, surgical interventions, and of chronic medication use were observed up to the age of 2 years. Subgroup analysis showed that growth parameters were not affected by the cycle protocol or strategy at any age. Our study indicated that embryo vitrification is associated with higher birthweight, even after controlling for confounders. However, in early childhood, anthropometry and weight and height gain was not different in children born after vitrified or fresh embryo transfer.

Maternal Midpregnancy Plasma trans 18:1 Fatty Acid Concentrations Are Positively Associated with Risk of Maternal Vascular Complications and Child Low Birth Weight

Background: Evidence is plentiful that trans fatty acids (TFAs) induce vascular inflammation with adverse metabolic consequences. However, it is not clear whether TFAs increase the risk of vascular pregnancy complications such as preeclampsia.Objective: We investigated associations between midpregnancy maternal plasma trans 18:1 fatty acid (t18:1) concentrations and pregnancy course and outcomes.Methods: Participants were 6695 pregnant women and newborns from the Generation R Study, Rotterdam, Netherlands (enrollment in 2001-2005). Maternal midpregnancy (mean ± SD gestational age: 20.7 ± 1.2 wk) t18:1 plasma concentrations were determined and related to gestational age and sex-adjusted birth weight SD scores, placental weight, and the risk of preeclampsia. In addition, we explored potential time trends by testing the association of maternal plasma t18:1 concentrations with birth weight in birth cohorts given the Dutch industry-initiative to lower food TFA contents during the inclusion period. Multiple logistic and linear regression analyses were performed, taking various socioeconomic and biological covariates into account.Results: A higher midpregnancy maternal plasma t18:1 concentration was associated with lower birth weight (SD score, adjusted β: -0.10; 95% CI: -0.15, -0.04; P < 0.001) and placental weight (kilograms, adjusted β: -10,65; 95% CI: -20.23, -1.07; P = 0.03) and with a higher risk of preeclampsia (adjusted OR: 1.65; 95% CI: 1.10, 2.49; P = 0.02). We observed a 31% decrease in the median plasma t18:1 concentration in our population over time, but the association between the plasma t18:1 concentration standardized per birth year and birth weight was comparable between birth-year cohorts (years 2001-2005).Conclusions: A higher maternal midpregnancy plasma t18:1 concentration was associated with lower birth weight and placental weight and with a higher risk of preeclampsia. Although the intake of TFAs in our population decreased during the inclusion period, the association with adverse pregnancy outcomes was unchanged even at lower maternal plasma t18:1 concentrations.

Ophthalmological outcome of 6.5 years children treated for retinopathy of prematurity: a Swedish register study

AimsTo determine the ophthalmological outcome at 6.5 years of age in children treated for retinopathy of prematurity (ROP), and registered in the national Swedish National Register for ROP register.MethodsData on...

Dietary patterns before and during pregnancy and small for gestational age in Japan: a prospective birth cohort study

BackgroundAlthough small for gestational age (SGA) is a serious problem worldwide, the association of dietary patterns before and during pregnancy with SGA risk is unclear. We evaluated this association among Japanese pregnant women using three methods: reduced rank regression (RRR) and partial least squares (PLS), methods for extracting dietary patterns that can explain the variation of response variables, and principal component analysis (PCA), a method for extracting dietary patterns of the population.MethodsBetween July 2013 and March 2017, 22,493 pregnant women were recruited to the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, a population-based prospective birth cohort study in Japan. Information on dietary intake was obtained using food frequency questionnaires, and dietary patterns were extracted using RRR, PLS, and PCA. Information on birth weight was obtained from obstetric records, and the birth weight SD score and SGA were defined by the method of the Japan Pediatric Society. The associations of dietary patterns with birth weight SD score and SGA risk were investigated using multiple linear regression and multiple logistic regression, respectively.ResultsA total of 17,728 mother-child pairs were included. The birth weight SD score was 0.15 ± 0.96, and the prevalence of SGA was 6.3%. The dietary patterns extracted by RRR and PLS were similar and characterized by a high intake of cereals and fruits and a low intake of alcoholic and non-alcoholic beverages in both pre- to early pregnancy and from early to mid-pregnancy. Higher adoption of the RRR and PLS patterns in both periods was associated with an increased birth weight SD score and lower risk of SGA. In contrast, the PCA1 pattern was not associated with birth weight SD score or SGA risk in either period. Although the PCA2 pattern was associated with increased birth weight SD score from early to mid-pregnancy, no other associations with birth weight SD score or SGA risk were observed.ConclusionsThe dietary pattern with a high intake of cereals and fruits and a low intake of alcoholic and non-alcoholic beverages before and during pregnancy was associated with a decreased SGA risk in Japan.

Analysis of Brain Injury Biomarker Neurofilament Light and Neurodevelopmental Outcomes and Retinopathy of Prematurity Among Preterm Infants

Circulating levels of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) are important in the course of brain injury in adults, but longitudinal postnatal circulating levels in preterm infants have not been investigated. To examine postnatal longitudinal serum levels of NfL and GFAP in preterm infants during the first 15 weeks of life and to explore possible associations between these biomarkers, neonatal morbidities, and neurodevelopmental outcomes at 2 years. This cohort study used data from 3 clinical studies, including 221 infants born before 32 weeks gestational age (GA) from 1999 to 2015; neurodevelopmental outcomes were evaluated in 120 infants. Data were collected at tertiary-level neonatal intensive care units in Gothenburg, Lund, and Uppsala, Sweden. Data analysis was conducted from January to October 2020. Preterm birth. Serum NfL and GFAP levels, retinopathy of prematurity (ROP), intraventricular hemorrhage, and Bayley Scales of Infant Development II and III at 2 years of age, analyzed by multivariate logistic regression measured by odds ratio (OR), and receiver operating characteristic curve (ROC) analysis. Area under the curve (AUC) was also measured. The 221 included infants (108 [48.9%] girls) had a mean (SD) GA at birth of 26.5 (2.1) weeks and a mean (SD) birth weight of 896 (301) grams. NfL levels increased after birth, remaining high during the first 4 weeks of life before declining to continuously low levels by postnatal age 12 weeks (median [range] NfL level at birth: 58.8 [11.5-1371.3] ng/L; 1 wk: 83.5 [14.1-952.2] ng/L; 4 wk: 24.4 [7.0-306.0] ng/L; 12 wk: 9.1 [3.7-57.0] ng/L). In a binary logistic regression model adjusted for GA at birth, birth weight SD score, Apgar status at 5 minutes, and mode of delivery, the NfL AUC at weeks 2 to 4 was independently associated with any ROP (OR, 4.79; 95% CI, 2.17-10.56; P < .001). In an exploratory analysis adjusted for GA at birth and sex, NfL AUC at weeks 2 to 4 was independently associated with unfavorable neurodevelopmental outcomes at 2 years corrected age (OR per 10-unit NfL increase, 1.07; 95% CI, 1.02-1.13; P = .01). Longitudinal GFAP levels were not significantly associated with neonatal morbidity or neurodevelopmental outcome. In this study, high NfL levels during the first weeks of life were associated with ROP and poor neurodevelopmental outcomes at 2 years of age. Associations between NfL and later neurovascular development in infants born prematurely should be investigated further.

CopenFast trial: Faster-acting insulin Fiasp versus insulin NovoRapid in the treatment of women with type 1 or type 2 diabetes during pregnancy and lactation - a randomised controlled trial

IntroductionFaster-acting insulin aspart (Fiasp) is approved for use in pregnancy and lactation, but no clinical study has evaluated its effects during this life stage in women with pre-existing diabetes. The...

Pregnancy outcomes according to the definition of gestational diabetes

ObjectiveTo assess the frequency and perinatal outcomes of gestational diabetes mellitus (GDM) defined by the criteria according to the International Association of Diabetes in Pregnancy Study Group (IADPSG) and the National Institute for Health and Care Excellence (NICE) diagnostic criteria for GDM.DesignA retrospective cohort study.SettingSix secondary and tertiary delivery hospitals in Finland in 2009.PopulationPregnant women (N = 4,033) and their offspring.MethodsWe used data on comprehensive screening of pregnant women with a 2-h 75-g oral glucose tolerance test (OGTT), performed between gestational weeks 24 and 40. OGTT glucose concentrations were used to identify women who fulfilled IADPSG and NICE criteria. While cut-offs according to Finnish national criteria partly overlapped with both criteria, a subgroup of IADPSG- or NICE-positive GDM women remained undiagnosed by Finnish criteria and hence non-treated. They were analysed as subgroups and compared to controls who were negative with all cut-offs.Main outcome measuresGDM prevalence, birth weight SD score (BWSDS), large for gestational age (LGA) and caesarean section (CS) rates.ResultsAmong the 4,033 women screened for GDM, 1,249 (31.0%) and 529 (13.1%) had GDM according to the IADPSG and NICE criteria, respectively. The LGA rate was similar in both groups. Regardless of the diagnostic criteria, women with GDM had a higher risk of induced delivery and CSs than controls. In IADPSG-positive non-treated women, offspring’s BWSDS and CS rate were higher than in controls.ConclusionsGDM prevalence was 2.4-fold higher according to the IADPSG compared with the NICE criteria but the LGA rate did not differ. BWSDS and CS rate were increased already with mild untreated hyperglycaemia.

Both glycaemic control and insulin dose during pregnancy in women with type 1 diabetes are associated with neonatal anthropometric measures and placental weight.

To investigate longitudinal associations of maternal glucose/HbA1c and insulin dose with birthweight-related outcomes in women with type 1 diabetes. We performed a cohort study including 473 pregnant women with type 1 diabetes with singleton pregnancies. We investigated maternal self-monitored blood glucose (SMBG, mmol/L), HbA1c (%, mmol/mol) and insulin dose (IU/kg/day) in the three trimesters as potential independent variables, while adjusting for potential confounders. Outcomes of interest were birthweight, birthweight SD score, neonatal length, weight/length index, ponderal index and placental weight. Multiple linear regression analysis was performed with separate analyses for SMBG and HbA1c . Maternal glucose and insulin dose were independently associated with birthweight-related outcomes. In the main analysis, in the first trimester most associations were positive for insulin dose, in the second the associations were positive for glucose and inverse for insulin while in the third there were no associations. Most sensitivity analyses produced consistent results. In a sensitivity analysis splitting the first trimester in two periods, positive associations of maternal insulin with birthweight-related outcomes were observed in weeks 0+ to 6+. Early in pregnancy in women with type 1 diabetes, maternal insulin dose is positively associated with birthweight-related outcomes, whereas in the second trimester, a positive association with SMBG emerges and the association with maternal insulin becomes inverse. If confirmed in other cohorts, these results would have implications in the management of women with type 1 diabetes.

Reduced size at birth and persisting reductions in adiposity in recent, compared with earlier, cohorts of infants born to mothers with gestational diabetes mellitus

Aims/hypothesisThis study aimed to explore the infancy growth trajectories of ‘recent’ and ‘earlier’ offspring of mothers with gestational diabetes mellitus (OGDM), each compared with the same control infants, and investigate whether ‘recent’ OGDM still exhibit a classical phenotype, with macrosomia and increased adiposity.MethodsWithin a prospective observational birth cohort, 98 ‘earlier’ OGDM born between 2001 and 2009 were identified using 75 g oral glucose tolerance testing at 28 weeks gestation, 122 recent OGDM born between 2011 and 2013 were recruited postnatally through antenatal diabetes clinics, and 876 normal birthweight infants of mothers with no history of diabetes were recruited across the full study period as the control group. All infants followed the same study protocol (measurements at birth, 3, 12 and 24 months, including weight, length and skinfold thickness indicating adiposity, and detailed demographic data). In all cases, GDM was defined using the International Association of Diabetes and Pregnancy Study Group criteria.ResultsEarlier OGDM had higher birthweight SD scores (SDS) than control infants. Conversely, recent OGDM had similar birthweight- and length SDS to control infants (mean ± SD, 0.1 ± 1.0 and− 0.1 ± 0.9, respectively), but lower mean skinfold thickness SDS (−0.4 ± 0.6 vs 0.0 ± 0.9; p < 0.001). After birth, earlier OGDM showed reduced gains in weight and length between 3 and 12 months. In contrast, recent OGDM had increased weight and skinfold thickness gains until 3 months, followed by reduced gains in those variables from 3 to 12 months, compared with control infants. At 24 months, recent OGDM had lower adiposity than control infants (mean skinfold thickness SDS −0.3 ± 0.7 vs 0.0 ± 0.8; p < 0.001). At all time points recent OGDM had lower growth measurements than earlier OGDM.Conclusions/interpretationRecent OGDM showed different growth trajectories to the earlier group, namely normalisation of birthweight and reduced adiposity at birth, followed by initial rapid weight gain but subsequent reduced adiposity postnatally. While avoidance of macrosomia at birth may be advantageous, the longer-term health implications of these changing growth trajectories are uncertain.

Phenotypic Features and Response to GH Treatment of Patients With a Molecular Defect of the IGF-1 Receptor.

The phenotype and response to GH treatment of children with an IGF1R defect is insufficiently known. To develop a clinical score for selecting children with short stature for genetic testing and evaluate the efficacy of treatment. Case series with an IGF1R defect identified in a university genetic laboratory. Of all patients with sufficient clinical data, 18 had (likely) pathogenic mutations (group 1) and 7 had 15q deletions including IGF1R (group 2); 19 patients were treated with GH. Phenotype and response to GH treatment. In groups 1 and 2, mean (range) birth weight, length, and head circumference (HC) SD scores (SDSs) were -2.1 (-3.7 to -0.4), -2.7 (-5.0 to -1.0), and -1.6 (-3.0 to 0.0), respectively. At presentation, height, HC, and serum IGF-1 SDSs were -3.0 (-5.5 to -1.7), -2.5 (-4.2 to -0.5), and +1.2 (-1.3 to 3.2), respectively. Feeding problems were reported in 15 of 19 patients. A clinical score with 76% sensitivity is proposed. After 3 years of GH treatment [1.1 (0.2) mg/m2/d] height gain in groups 1 (n = 12) and 2 (n = 7) was 0.9 SDS and 1.3 SDS (at a mean IGF-1 of 3.5 SDS), less than reported for small for gestational age (1.8 SDS). A clinical score encompassing birth weight and/or length, short stature, microcephaly, and IGF-1 is useful for selecting patients for IGF1R analysis. Feeding problems are common and the growth response to GH treatment is moderate.

Dynamic prediction of childhood high blood pressure in a population-based birth cohort: a model development study

ObjectivesTo develop a dynamic prediction model for high blood pressure at the age of 9–10 years that could be applied at any age between birth and the age of 6...

The impact of restricted gestational weight gain by dietary intervention on fetal growth in women with gestational diabetes mellitus.

We aimed to investigate the impact of maternal gestational weight gain (GWG) during dietary treatment on fetal growth in pregnancies complicated by gestational diabetes (GDM). This was a retrospective cohort study of 382 women consecutively diagnosed with GDM before 34weeks' gestation with live singleton births in our centre (Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark) between 2011 and 2017. The women were stratified into three groups according to restricted (53%), appropriate (16%) and excessive (31%) weekly GWG during dietary treatment (using the Institute of Medicine guidelines) to estimate compliance with an energy-restricted 'diabetes diet' (6000kJ/day [1434kcal/day], with approximately 50% of energy intake coming from carbohydrates with a low glycaemic index, and a carbohydrate intake of 175g/day). Insulin therapy was initiated if necessary, according to local clinical guidelines. Glucose tolerance, HbA1c, weekly GWG before dietary treatment (difference between weight at GDM diagnosis and pre-pregnancy weight, divided by the number of weeks) and SD score for fetal abdominal circumference were comparable across the three groups at diagnosis of GDM at 276 ± 51weeks (gestation time is given as weeksdays). The women were followed for 100 ± 51weeks, during which 54% received supplementary insulin therapy and the average (mean) GWG during dietary treatment was 0kg, 3kg and 5kg in the three groups, respectively. Excessive weekly GWG during dietary treatment, reflecting poor dietary adherence was associated with increasing HbA1c (p = 0.014) from diagnosis of GDM to late pregnancy and infants with a birthweight-SD score of 0.59 ± 1.6. In contrast, restricted weekly GWG during dietary treatment, reflecting strict dietary adherence, was associated with decreasing HbA1c (p = 0.001) from diagnosis of GDM to late pregnancy and infants with a birthweight-SD score of 0.15 ± 1.1, without increased prevalence of infants born small for gestational age. Excessive GWG during dietary treatment and late-pregnancy HbA1c were identified as potentially modifiable clinical predictors of infant birthweight-SD score (p = 0.02 for both variables) after correction for confounders. Restricted GWG during dietary treatment was associated with healthier fetal growth in women with GDM. GWG during dietary treatment and late-pregnancy HbA1c were identified as potentially modifiable clinical predictors of infant birthweight-SD score.

The effect of hypoglycaemia on neurocognitive outcome in children and adolescents with transient or persistent congenital hyperinsulinism.

To examine the hypoglycaemic effect on neurodevelopmental outcome in patients with transient and persistent congenital hyperinsulinism (CHI) born in the 21st century. A cohort of 117 patients (66 males, 51 females) with CHI aged 5 to 16years (mean age 8y 11mo, SD 2y 7mo) were selected from a Finnish nationwide registry to examine all the patients with similar methods. Neurodevelopment was first evaluated retrospectively. The 83 patients with no risk factors for neurological impairment other than hypoglycaemia were recruited and 44 participated (24 males, 20 females; mean age 9y 7mo, SD 3y 1mo) in neuropsychological assessment with the Wechsler Intelligence Scale for Children, Fourth Edition and the Finnish version of the Developmental Neuropsychological Assessment, Second Edition domains of attention, language, memory, sensorimotor, and visual functioning. In retrospective analysis, transient and persistent CHI groups had similar prevalences of mild (22% and 18% respectively) or severe (5% and 7% respectively) neurodevelopmental difficulties. In clinical assessment, the neurocognitive profile was within the average range in both groups, but children with persistent CHI showed significant but restricted deficits in attention, memory, visual, and sensorimotor functions compared with the general population. The transient CHI group did not differ from the standardization samples. Besides the more apparent broader neurological deficits, children with persistent CHI have an increased risk for milder specific neurocognitive problems, which should be considered in the follow-up. Children with persistent congenital hyperinsulinism showed deficits in attention, memory, visual, and sensorimotor functions. The deficits were potentially of hypoglycaemic origin. Children with transient hyperinsulinism did not differ from the general population.

The Impact of Restricted Gestational Weight Gain on Fetal Growth during Dietary Treatment in Women with Gestational Diabetes Mellitus

Aim: To investigate the impact of maternal gestational weight gain during dietary treatment (GWG-diet) on fetal growth in pregnancies complicated by gestational diabetes (GDM). Material and Methods: A retrospective cohort study of 382 consecutive women diagnosed with GDM &amp;lt;34 weeks and live singleton births in our center in 2011-2017. The women were stratified according to restricted (53%), appropriate (17%) and excessive (31%) weekly GWG-diet (Institute of Medicine guidelines) to estimate compliance to a calorie-restricted diabetes diet (1700 kcal daily). Insulin therapy was initiated according to local clinical guidelines. Results: Glucose tolerance, HbA1c, GWG before dietary treatment (GWG-before) and fetal abdominal circumference standard deviation (SD) score were comparable across the three GWG-diet groups at referral at 276±51 weeks. The women were followed for 100 ±51 weeks, 54% received insulin therapy and the average GWG-diet in the three groups was 0 kg, 3 kg and 5 kg, respectively. Women with excessive weekly GWG-diet, also had increasing HbA1c (p=0.014) during dietary treatment and infants with a birth weight SD-score of 0.59 ±1.6, while women with restricted weekly GWG-diet also had decreasing HbA1c (p=0.001) during dietary treatment, and infants with a birth weight SD-score of 0.15 ±1.1, without intrauterine growth restriction. Excessive GWG-diet and late pregnancy HbA1c were predictors of infant birth weight SD-score (p&amp;lt;0.001) after correction for parity, uptake area, pre-pregnancy BMI and insulin therapy. Conclusion: Restricted GWG-diet was associated with more appropriate fetal growth in women with GDM. GWG-diet and late pregnancy HbA1c were modifiable clinical predictors of infant birth weight SD-score. Disclosure L. Kurtzhals: None. S. Nørgaard: None. H. Ronneby: None. A.L. Secher: None. A. Tabor: None. H. McIntyre: Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Danish Diabetes Academy. P. Damm: Advisory Panel; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. E.R. Mathiesen: Speaker's Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S, Novo Nordisk Foundation, Novo Nordisk A/S.

Associations of Dehydroepiandrosterone Sulfate With Cardiometabolic Risk Factors in Prepubertal Children.

Premature adrenarche (PA) has been associated with overweight and insulin resistance, but the associations of serum dehydroepiandrosterone sulfate (DHEAS) concentration with other cardiometabolic risk factors are uncertain. To examine the associations of serum DHEAS concentration with several cardiometabolic risk factors in children. Cross-sectional data from the Physical Activity and Nutrition in Children Study. Population sample of 207 girls and 225 boys aged 7.6 ± 0.4 years. Cardiometabolic risk factors by serum DHEAS concentration. DHEAS correlated positively with body mass index standard deviation score, body fat percentage, lean body mass, high-sensitivity C-reactive protein (hs-CRP), and alanine aminotransferase (ALT) when adjusted for age and sex. The associations of DHEAS with hs-CRP and ALT disappeared when adjusted also for body fat percentage. When further adjusted for birth weight SD score, DHEAS correlated negatively with low-density lipoprotein (LDL) cholesterol and LDL/high-density lipoprotein (HDL) cholesterol ratio. LDL cholesterol was lower in children with DHEAS ≥40 µg/dL than in those with DHEAS <40 µg/dL, adjusted for age, sex, and body fat percentage (86.5 vs 92.3 mg/dL, P = 0.029). This association strengthened after further adjustment for birth weight SD score (85.3 vs 92.3 mg/dL, P = 0.012). Higher DHEAS is not associated with an increased cardiometabolic risk in prepubertal children. Instead, it may be protective, evidenced by an association with lower LDL cholesterol and LDL/HDL cholesterol ratio. The increased cardiometabolic risk in PA shown in many studies may be due to low birth weight and childhood overweight associated with PA.

Outcome of Twin Pregnancies Complicated by a Neural Tube Defect.

Twin pregnancies discordant for neural tube defects (NTD) is a management dilemma. Risks of preterm delivery from polyhydramnios must be balanced with the risks of selective termination (ST) of the anomalous fetus. We investigated the prevalence of twin pregnancies discordant for NTD and the rate of pregnancy complications in our institution over a 10-year period. Cases were obtained by searching the hospital ultrasound database and findings were confirmed by expert review of ultrasound images. Outcomes of ST and expectant management were assessed. Each unaffected co-twin was assigned to three consecutive twin pregnancy controls matched by chorionicity and maternal age. Primary outcome was birth before 34 weeks' gestation. Secondary outcomes were small for gestational age, mode of delivery, neonatal unit admission, and neonatal death. In total, 13 pregnancies were identified as potential cases. Of these, 11 were included in the analysis: 9 dichorionic diamniotic and 2 monochorionic diamniotic twins. Seven cases had ST and four were managed expectantly. We found 100% (4/4) of expectantly managed pregnancies delivered <34 weeks compared with 14% (1/7) of the ST group (p = .015). Polyhydramnios complicated three expectantly managed pregnancies and one pregnancy in the ST group. The birthweight SD score of all unaffected co-twins was ≥-2. The case-control analysis showed a higher rate of polyhydramnios in twin pregnancies discordant for NTD compared with controls, but little evidence for differences between groups in delivery rates <34 weeks, birthweight, neonatal unit admission, or neonatal death. ST warrants serious consideration to avoid potential complications to the unaffected co-twin.

The placental imprinted DLK1-DIO3 domain: a new link to prenatal and postnatal growth in humans

The developmentally important DLK1-DIO3 imprinted domain on human chromosome 14 is regulated by 2 differentially methylated regions, the intergenic differentially methylated region and the MEG3 differentially methylated region. The aim was to determine the natural variation in DNA methylation at these differentially methylated regions in human placentas, and to determine its link to gene expression levels at the domain. The second goal was to explore whether the domain's methylation and gene expression correlate with prenatal and early postnatal growth of the conceptus. Using pyrosequencing, we determined methylation levels at CpG dinucleotides across the 2 regulatory differentially methylated regions in placentas from 91 healthy mothers. At birth, placentas and infants were weighed (gestational age 39 ± 1 weeks; birthweight SD score 0.1 ± 0.8) and placental biopsies were collected. RNA expression was quantitated by real-time polymerase chain reaction. Infants' weights and lengths were followed up monthly during the first year. Methylation levels at the 2 regulatory differentially methylated regions were linked and varied considerably between placentas. MEG3 promoter differentially methylated region methylation correlated negatively with weight increase (β= -0.406, P= .001, R2= 0.206) andlength increase (β= -0.363, P= .002, R2= 0.230) during the firstpostnatal year. The methylation level of the intergenic differentially methylated region correlated with DIO3 expression (β= 0.313, P= .032, R2= 0.152). Furthermore, the expression of both DIO3 and RTL1 (bothimprinted genes within the DLK1-DIO3 domain) was negatively associated with birthweight (β= -0.331, P= .002, R2= 0.165; and β=-0.307, P= .005, R2= 0.159, respectively). RTL1 expression, in addition, was negatively linked to birth length (β= -0.306, P= .007, R2= 0.162). Our combined findings strongly suggest that placental DNA methylation at the DLK1-DIO3 domain's intergenic differentially methylated region and MEG3 promoter differentially methylated region relates to measures of early human growth, and may thus contribute to its control.