Long-term weight development in offspring exposed to obesity in pregnancy

The prevalence of childhood overweight has increased drastically, and weight development in preschool years is linked to future obesity. A greater risk of overweight at preschool age is conferred by a higher maternal preconception body mass index (BMI), an urgent public health issue, since overweight or obesity occurs in up to two-thirds of child-bearing women today, frequently developing metabolic complications. In fact, our research group previously found that women with obesity may develop dysglycemia towards the end of pregnancy, despite a negative test for gestational diabetes (GDM). Therefore, we hypothesized that late-pregnancy dysglycemia could also contribute to adverse longitudinal BMI development in their offspring. For prevention, such offspring should be identified at a time prior to the first upper divergence in BMI gain in the trajectory towards overweight manifestation. However, prediction of early deviations in weight gain has not been achieved on an individual level as a prerequisite for implementation in the public health setting, because data on weight trajectories in children who had exposure to gestational overnutrition and the contribution of “obesogenic influences” are lacking. Using comprehensive and longitudinal data from different gestational and postnatal phases of the large Programming of Enhanced Adiposity Risk in CHildhood - Early Screening (PEACHES) cohort study of women with obesity and their children (n = 1,707), we performed linear mixed-effects models and mediation analysis to evaluate the long-term (from age 2 to 4 years) effect and contribution of obesity-related dysglycemia at the end of gestation (women’s HbA1c [glycated hemoglobin] at delivery ≥5.7%) on preschool BMI (at 4 years of age), respectively. We also identified specific patterns of BMI growth from birth until 5 years of age following exposure to obesity in pregnancy, assessed various BMI outcomes, and evaluated their underlying contributors in offspring using k-means cluster analysis and a series of multivariable regression models. Subsequently, a serial approach of individual risk score assessment, prediction, and re-assessments was developed using penalized logistic regressions. Data from an independent mother-child cohort (PErinatal Prevention of Obesity [PEPO], n = 11,730) were available for data validation. In the analysis of children exposed to gestational obesity, a diagnosis of GDM did not influence offspring BMI at age 4 years. However, within the group of mothers with obesity who tested negative for GDM towards the end of the second trimester, dysglycemia in late pregnancy was associated with high BMI gains between ages 2 and 4 years in offspring (mean annual increment Δ 0.18, 95% confidence interval [CI] 0.06–0.30). Overall, it accounted for almost one-quarter of the contribution of gestational obesity on offspring BMI z-score at age 4 years. In these mothers, the presence of late-pregnancy dysglycemia was related to a risk of prediabetes or type 2 diabetes (T2D) a few years later that was four times higher than in mothers with normal HbA1c at delivery (relative risk [RR] 4.01, 95% CI 1.97–8.17). Excessive third-trimester weight gain was related to a mean increase in the risk of dysglycemia in late pregnancy by 72% (RR 1.72, 95% CI 1.12–2.65) in mothers with obesity who had a negative GDM test. Next, we focused on a “pre-symptomatic” offspring BMI outcome and identified a “high-risk” subgroup of children (21%) likely to undergo early upper divergence from a healthy BMI growth track after exposure to gestational overnutrition. Belonging to this upper BMI cluster was associated with a high risk of preschool overweight/obesity (odds ratio [OR] 16.13; 95% CI 9.98–26.05). Underlying pre- and perinatal influences such as high maternal weight gain (OR 2.08, 95% CI 1.25–3.45) and smoking in pregnancy (OR 1.94, 95% CI 1.27–2.95) were essential to predict a subsequent “higher-than-normal BMI growth” pattern in the 3-month-old, 1-year-old, and 2-year-old offspring. Sequential prediction models showed adequate predictive performances (area under the receiver operating characteristic [AUROC] 0.69–0.79, specificity 64.7–78.1%, sensitivity 70.7–76.0%), and findings were confirmed in the cohort PEPO. In conclusion, in order to achieve healthy weight development at the beginning of life, efforts should be made to optimize maternal weight gain and glucose metabolism as well as fetal growth also in the 3rd trimester of pregnancy, particularly if the mother with obesity had a prior GDM-negative test result. After birth, children of women with obesity should be closely sequentially assessed for risk quantification and individual detection of an increased risk of “higher-than-normal” BMI growth at the established well-child care visits for intensified prevention measures. A “continuum” of targeted management strategies in the very early stages of life could help reduce intergenerational transmission of obesity

Factors influencing the success and complications of intraosseous access in pediatric patients—a prospective nationwide surveillance study in Germany

BackgroundVascular access is essential for the efficient treatment of critically ill children, but it can be difficult to obtain. Our study was conducted to analyze the feasibility and short-term safety of intraosseous access (IO) use as well as factors influencing its success and the incidence of complications in pediatric emergencies and resuscitation. This dataset of systematically documented intraosseous access attempts constitutes one of the largest published in the literature.MethodsTwo-year nationwide prospective surveillance study in Germany from July 2017 to June 2019. Pediatric hospitals anonymously reported the case data of all children aged 28 days to 18 years who arrived with or were treated with an intraosseous access to the German Pediatric Surveillance Unit (GPSU). The main outcomes were the occurrence of complications, overall success and success at the first attempt. The influence of individual factors on outcomes was evaluated using multivariate regression models.ResultsA total of 417 patients underwent 549 intraosseous access attempts. The overall rates of success and success at the first attempt were 98.3% and 81.9%, respectively. Approximately 63.6% of patients were successfully punctured within 3 min from the time of indication. Approximately 47.7% of IO access attempts required patient resuscitation. Dislocation [OR 17.74 (5.32, 59.15)] and other complications [OR 9.29 (2.65, 32.55)] occurred more frequently in the prehospital environment. A total of 22.7% of patients experienced minor complications, while 2.5% of patients experienced potentially severe complications.ConclusionWe conclude that intraosseous access is a commonly used method for establishing emergency vascular access in children, being associated with a low (age-dependent) rate of severe complications and providing mostly reliable vascular access despite a relatively high rate of dislocation

Intraosseous access in neonates is feasible and safe – An analysis of a prospective nationwide surveillance study in Germany

BackgroundThis was a prospective surveillance study to investigate reports on the safety and frequency of use of intraosseous (IO) access in neonates.MethodsOver a two-year period, paediatric hospitals in Germany were asked to report all cases of IO access to the nationwide Surveillance Unit for Rare Paediatric Diseases (ESPED). Hospitals reporting a case submitted responses via an anonymised electronic questionnaire, providing details on indication, success rate, system used, location, duration to first successful IO access, complications, alternative access attempts and short-term outcome. We present a subset of data for IO use in infants of less than 28 days.ResultsA total of 161 neonates (145 term and 16 preterm born infants) with 206 IO access attempts were reported. In 146 neonates (91%), IO access was successfully established, and success was achieved with the first attempt in 109 neonates (75%). There was no significant impact of gestational age or provider’s educational level on success rates. In 71 infants with successful IO access (79%), the estimated duration of placement was less than 3 min. The proximal tibia was the predominant site used. A semiautomatic battery-driven device was used in 162 attempts (88%). The most often applied medications via IO access were crystalloid fluid and adrenaline. Potentially severe complications occurred in 9 patients (6%).ConclusionWithin this surveillance study, IO access in neonates was feasible and safe. IO access is an important alternative for vascular access in neonates

Predicting the earliest deviation in weight gain in the course towards manifest overweight in offspring exposed to obesity in pregnancy: a longitudinal cohort study

BACKGROUND: Obesity in pregnancy and related early-life factors place the offspring at the highest risk of being overweight. Despite convincing evidence on these associations, there is an unmet public health need to identify “high-risk” offspring by predicting very early deviations in weight gain patterns as a subclinical stage towards overweight. However, data and methods for individual risk prediction are lacking. We aimed to identify those infants exposed to obesity in pregnancy at ages 3 months, 1 year, and 2 years who likely will follow a higher-than-normal body mass index (BMI) growth trajectory towards manifest overweight by developing an early-risk quantification system. METHODS: This study uses data from the prospective mother-child cohort study Programming of Enhanced Adiposity Risk in CHildhood–Early Screening (PEACHES) comprising 1671 mothers with pre-conception obesity and without (controls) and their offspring. Exposures were pre- and postnatal risks documented in patient-held maternal and child health records. The main outcome was a “higher-than-normal BMI growth pattern” preceding overweight, defined as BMI z-score >1 SD (i.e., World Health Organization [WHO] cut-off “at risk of overweight”) at least twice during consecutive offspring growth periods between age 6 months and 5 years. The independent cohort PErinatal Prevention of Obesity (PEPO) comprising 11,730 mother-child pairs recruited close to school entry (around age 6 years) was available for data validation. Cluster analysis and sequential prediction modelling were performed. RESULTS: Data of 1557 PEACHES mother-child pairs and the validation cohort were analyzed comprising more than 50,000 offspring BMI measurements. More than 1-in-5 offspring exposed to obesity in pregnancy belonged to an upper BMI z-score cluster as a distinct pattern of BMI development (above the cut-off of 1 SD) from the first months of life onwards resulting in preschool overweight/obesity (age 5 years: odds ratio [OR] 16.13; 95% confidence interval [CI] 9.98–26.05). Contributing early-life factors including excessive weight gain (OR 2.08; 95% CI 1.25–3.45) and smoking (OR 1.94; 95% CI 1.27–2.95) in pregnancy were instrumental in predicting a “higher-than-normal BMI growth pattern” at age 3 months and re-evaluating the risk at ages 1 year and 2 years (area under the receiver operating characteristic [AUROC] 0.69–0.79, sensitivity 70.7–76.0%, specificity 64.7–78.1%). External validation of prediction models demonstrated adequate predictive performances. CONCLUSIONS: We devised a novel sequential strategy of individual prediction and re-evaluation of a higher-than-normal weight gain in “high-risk” infants well before developing overweight to guide decision-making. The strategy holds promise to elaborate interventions in an early preventive manner for integration in systems of well-child care. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02318-z

Late-pregnancy dysglycemia in obese pregnancies after negative testing for gestational diabetes and risk of future childhood overweight: An interim analysis from a longitudinal mother-child cohort study

BACKGROUND Maternal pre-conception obesity is a strong risk factor for childhood overweight. However, prenatal mechanisms and their effects in susceptible gestational periods that contribute to this risk are not well understood. We aimed to assess the impact of late-pregnancy dysglycemia in obese pregnancies with negative testing for gestational diabetes mellitus (GDM) on long-term mother-child outcomes. METHODS AND FINDINGS The prospective cohort study Programming of Enhanced Adiposity Risk in Childhood-Early Screening (PEACHES) (n = 1,671) enrolled obese and normal weight mothers from August 2010 to December 2015 with trimester-specific data on glucose metabolism including GDM status at the end of the second trimester and maternal glycated hemoglobin (HbA1c) at delivery as a marker for late-pregnancy dysglycemia (HbA1c \geq 5.7% 39 mmol/mol). We assessed offspring short- and long-term outcomes up to 4 years, and maternal glucose metabolism 3.5 years postpartum. Multivariable linear and log-binomial regression with effects presented as mean increments (\textgreek{D}) or relative risks (RRs) with 95{\%} confidence intervals (CIs) were used to examine the association between late-pregnancy dysglycemia and outcomes. Linear mixed-effects models were used to study the longitudinal development of offspring body mass index (BMI) z-scores. The contribution of late-pregnancy dysglycemia to the association between maternal pre-conception obesity and offspring BMI was estimated using mediation analysis. In all, 898 mother-child pairs were included in this unplanned interim analysis. Among obese mothers with negative testing for GDM (n = 448), those with late-pregnancy dysglycemia (n = 135, 30.1{\%}) had higher proportions of excessive total gestational weight gain (GWG), excessive third-trimester GWG, and offspring with large-for-gestational-age birth weight than those without. Besides higher birth weight (\textgreek{D} 192 g, 95{\%} CI 100-284) and cord-blood C-peptide concentration (\textgreek{D} 0.10 ng/ml, 95{\%} CI 0.02-0.17), offspring of these women had greater weight gain during early childhood (\textgreek{D} BMI z-score per year 0.18, 95{\%} CI 0.06-0.30, n = 262) and higher BMI z-score at 4 years (\textgreek{D} 0.58, 95{\%} CI 0.18-0.99, n = 43) than offspring of the obese, GDM-negative mothers with normal HbA1c values at delivery. Late-pregnancy dysglycemia in GDM-negative mothers accounted for about one-quarter of the association of maternal obesity with offspring BMI at age 4 years (n = 151). In contrast, childhood BMI z-scores were not affected by a diagnosis of GDM in obese pregnancies (GDM-positive: 0.58, 95{\%} CI 0.36-0.79, versus GDM-negative: 0.62, 95{\%} CI 0.44-0.79). One mechanism triggering late-pregnancy dysglycemia in obese, GDM-negative mothers was related to excessive third-trimester weight gain (RR 1.72, 95{\%} CI 1.12-2.65). Furthermore, in the maternal population, we found a 4-fold (RR 4.01, 95{\%} CI 1.97-8.17) increased risk of future prediabetes or diabetes if obese, GDM-negative women had a high versus normal HbA1c at delivery (absolute risk: 43.2{\%} versus 10.5{\%}). There is a potential for misclassification bias as the predominantly used GDM test procedure changed over the enrollment period. Further studies are required to validate the findings and elucidate the possible third-trimester factors contributing to future mother-child health status. CONCLUSIONS Findings from this interim analysis suggest that offspring of obese mothers treated because of a diagnosis of GDM appeared to have a better BMI outcome in childhood than those of obese mothers who-following negative GDM testing-remained untreated in the last trimester and developed dysglycemia. Late-pregnancy dysglycemia related to uncontrolled weight gain may contribute to the development of child overweight and maternal diabetes. Our data suggest that negative GDM testing in obese pregnancies is not an {\textquotedbl}all-clear signal{\textquotedbl} and should not lead to reduced attention and risk awareness of physicians and obese women. Effective strategies are needed to maintain third-trimester glycemic and weight gain control among otherwise healthy obese pregnant women