Catch-up Growth In Infants Research Articles

Prospective cohort study on facial profile changes in infants with Robin sequence and healthy controls

BackgroundVarious conservative and surgical approaches exist to treat Robin sequence (RS), but their effects on facial profile and mandibular catch-up growth are unclear. A functional treatment concept, used in our centre for 25 years, includes an individualized palatal plate with a velo-pharyngeal extension and intensive feeding training.MethodsWe performed a prospective study to objectively describe facial profiles in infants with RS treated with the above concept. Infants with isolated RS were admitted to our tertiary perinatal and national referral centre for craniofacial malformations between May 2018 and Nov 2019. Infants with RS received 3D-photographs during clinically indicated visits. Healthy controls were recruited from Dec 2018 to Sep 2019 and received 3D-photographs every 3 months. The digitally measured jaw index (JI), defined as alveolar overjet (O) x maxillary arch (U)/mandibular arch (L), and the soft tissue reference points A’-point, Nasion’, B’-point angle (ANB’), describing the relative position of maxilla to mandible, were evaluated. Linear mixed models were used to examine time trajectories in JI and ANB’.ResultsA total of 207 3D images, obtained in 19 infants with RS and 32 controls, were analysed. JI and ANB’ decreased over time in both groups [for JI − 0.18 (95% CI − 0.25 to − 0.10); for ANB’: − 0.40° per month [(95% CI − 0.48 to − 0.32)]] but remained lower in controls [for JI − 2.5 (95% CI − 3.2 to − 1.8); for ANB’-1.7° (95% CI − 2.4 to − 1.0)]. Also, the ANB’ model showed a significant effect of the interaction term diagnosis x age.ConclusionsBased on longitudinal 3D images, we describe changes in objective parameters of facial profile in infants with and without RS during the first year of life. Our findings indicate catch-up growth in infants treated for RS.4YQYEi2Zb5vMP7WQ-MbtxwVideo

Should We Monitor Renal Functions in Congenital Heart Disease Infants Using High Energy Infant Formula? A Case Report

Background High Energy Infant Formula (HEIF) promotes adequate catch-up growth in infants with faltering growth. Of concern, is the potential increased risk of HEIF as a high protein diet on renal function. Case Presentation This four month old female presented with ventricular septal defect, pulmonary hypertension and heart failure that was controlled with treatment. She suffered from faltering growth where her weight and length were < -2 z-score for age thus HEIF was prescribed. Serum creatinine was high normal. Two weeks after HEIF intake, growth was still faltering and mild dyspnea reappeared inspite cardiac medications. Investigations showed a rising high serum creatinine. Abdominal ultrasound revealed the presence of a single kidney. The exact contribution of predisposing factors to renal dysfunction can’t be measured since the patient had an already borderline renal functions. Conclusion Renal functions should be monitored before HEIF and during its use to avoid renal dysfunction in susceptible patients.

Catch-Up Growth in Infants and Young Children With Faltering Growth: Expert Opinion to Guide General Clinicians.

Faltering growth (FG) is a problem regularly seen by clinicians in infants and young children (<2 years of age). It can occur due to non-disease-related and disease-related causes and is associated with a wide range of adverse outcomes, including shorter-term effects such as impaired immune responses and increased length of hospital stay, and longer-term consequences, including an impact on schooling and cognitive achievements, short stature, and socioeconomic outcomes. It is essential to detect FG, address underlying causes and support catch-up growth where this is indicated. However, anecdotal reports suggest misplaced fear of promoting accelerated (too rapid) growth may deter some clinicians from adequately addressing FG. An invited international group of experts in pediatric nutrition and growth reviewed the available evidence and guidelines on FG resulting from disease-related and non-disease-related effects on nutritional status in healthy term and small for gestational age infants and children up to the age of 2 years in low-, middle-, and high-income countries. Using a modified Delphi process, we developed practical consensus recommendations to provide clarity and practical recommendations for general clinicians on how FG should be defined in different young child populations at risk, how FG should be assessed and managed, and the role of catch-up growth after a period of FG. We also suggested areas where further research is needed to answer remaining questions on this important issue.

Associations between infant growth and pubertal onset timing in a multiethnic prospective cohort of girls

BackgroundEarly puberty increases risk of adverse health conditions throughout the life course. US girls are experiencing earlier puberty without clear reasons. Studies suggest early life factors, such as infant growth, may influence pubertal timing. We assessed the associations between infant growth and onset of breast development (thelarche), pubic hair development (pubarche), and menarche in girls.MethodsA prospective cohort of girls born at a Kaiser Permanente Northern California medical facility in 2005–11 was used. Weight-for-age z-scores were calculated at birth and 24 months. Difference in z-scores greater than 0.67 represent rapid “catch-up” growth, less than -0.67 represent delayed “catch-down” growth, and between -0.67 and 0.67 represent “normal” growth. Pubertal onset was measured using clinician-assessed sexual maturity ratings (SMRs) and defined as the age at transition from SMR 1 to SMR 2 + for both thelarche and pubarche. SMR data was collected through June 2020. Menarche was analyzed as a secondary outcome. Weibull and modified Poisson regression models were used. Models were adjusted for potential confounders.ResultsThere were 15,196 girls included in the study. Approximately 30.2% experienced catch-up growth, 25.8% experienced catch-down growth, and 44% had normal growth. Girls with catch-up growth had increased risk of earlier thelarche (hazard ratio = 1.26, 95% confidence interval (CI): 1.18, 1.35), pubarche (1.38, 95% CI: 1.28, 1.48), and menarche (< 12y, relative risk = 1.52, 95% CI: 1.36, 1.69) compared to those with normal growth, after adjusting for covariates. These associations were partially mediated by childhood body mass index. Catch-down growth was associated with later pubertal onset.ConclusionsGirls who experience infant catch-up growth have higher risk of earlier pubertal development compared to girls with normal growth and the associations are partially explained by childhood obesity. This information may help clinicians to monitor girls who are at high risk of developing earlier.

Patterns of Fetal and Infant Growth and Brain Morphology at Age 10 Years

Preterm birth and low birth weight are associated with brain developmental and neurocognitive outcomes in childhood; however, not much is known about the specific critical periods in fetal life and infancy for these outcomes. To examine the associations of fetal and infant growth patterns with brain morphology in children at school age. This population-based, prospective cohort study was conducted from February 1 to April 16, 2021, as a part of the Generation R Study in Rotterdam, the Netherlands. The study included 3098 singleton children born between April 1, 2002, and January 31, 2006. Fetal weight was estimated in the second and third trimesters of pregnancy by ultrasonography. Infant weight was measured at birth and at 6, 12, and 24 months. Fetal and infant weight acceleration or deceleration were defined as a change in SD scores greater than 0.67 between time points. Infant measurements also included peak weight velocity, and age and body mass index reached at adiposity peak. Brain structure, including global and regional brain volumes, was quantified by magnetic resonance imaging at age 10 years. The study evaluated 3098 children (mean [SD] age at follow-up, 10.1 [0.6] years; 1557 girls [50.3%]; and 1753 Dutch [57.8%]). One SD score-higher weight gain until the second and third trimesters, birth, and 6, 12, and 24 months was associated with larger total brain volume independently of growth during any other age windows (second trimester: 5.7 cm3; 95% CI, 1.2-10.2 cm3; third trimester: 15.3 cm3; 95% CI, 11.0-19.6 cm3; birth: 20.8 cm3; 95% CI, 16.4-25.1 cm3; 6 months: 15.6 cm3; 95% CI, 11.2-19.9 cm3; 12 months: 11.3 cm3; 95% CI, 7.0-15.6 cm3; and 24 months: 11.1 cm3; 95% CI, 6.8-15.4 cm3). Compared with children with normal fetal and infant growth, those with fetal and infant growth deceleration had the smallest total brain volume (-32.5 cm3; 95% CI, -53.2 to -11.9 cm3). Children with fetal weight deceleration followed by infant catch-up growth had similar brain volumes as children with normal growth. Higher peak weight velocity and body mass index reached at adiposity peak were associated with larger brain volumes. Similar results were observed for cerebral and cerebellar gray and white matter volumes. This cohort study's findings suggest that both fetal and infant weight growth might be critical for cerebral and cerebellar brain volumes during childhood. Whether these associations link to neurocognitive outcomes should be further studied.

Bone density and body composition in small for gestational age children with adequate catch up growth: A preliminary retrospective case control study

Fetal growth patterns and birth weight (BW) have been associated with bone mineral density (BMD) and content (BMC) throughout infancy and childhood up to early adulthood. We hypothesized that in small for gestational age (SGA) children, compensatory infant catch-up growth to normal height centiles counteracts the adverse consequences of low BW on bone accrual. To evaluate BMD and BMC of SGA children born at term who experienced a normal catch-up growth as compared to children born appropriate for gestational age (AGA). We recruited 53 SGA (26 females) and 60 AGA children (27 females), aged 6 to 18years, matched for sex and body mass index (BMI). Fat mass (FM); Free fat mass (FFM); Lumbar spine and Total body less head (TBLH) BMD; BMC and BMD standard deviation scores corrected for body size (BMAD, BMAD z-score and TBLH BMD/Height) and TBLH BMC for FFM (TBLHBMC/FFM) were derived from Dual Energy X-ray absorptiometry (DXA) scans. SGA and AGA children did not differ in any auxological, body composition and bone parameters appropriately adjusted for height and FFM. BMI, FM and, remarkably, FFM were significantly correlated with bone mass parameters in both groups while no correlation was found between FM and FFM with the BW SDS in the univariate analysis. Our preliminary data demonstrate that SGA children born at term who recover from their growth deficiency through catch-up growth achieve bone mass and body composition not different from children born AGA.

Effect of calorie-enriched formula on postoperative catch-up growth in infants with cyanotic congenital heart disease: a propective randomized controlled study

OBJECTIVE To study the effect of calorie-enriched formula on postoperative catch-up growth in infants with cyanotic congenital heart disease (CHD). METHODS A total of 100 infants with cyanotic CHD who underwent surgical operation from January to December, 2017, were randomly divided into a high-calorie group (receiving calorie-enriched formula after surgery) and a conventional group (receiving standard formula after surgery), with 50 infants in each group. All infants were followed up for 6 months. The observation indices included body height, body weight, prealbumin, and N-terminal pro-brain natriuretic peptide before surgery, at the time of ventilator weaning and extubation after surgery, and at 1, 3, and 6 months after surgery. Height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and weight-for-height Z-score (WHZ) were also assessed. Adverse reactions were recorded for both groups. RESULTS There were 25 cases (50%) and 21 cases (42%) of malnutrition in the high-calorie group and the conventional group respectively before surgery (P > 0.05). The nutritional status of the two groups improved 6 months after surgery (P < 0.05). At 6 months after surgery, compared with the conventional group, the high-calorie group had a lower proportion of infants with malnutrition (18% vs 36%, P < 0.05) and also a lower proportation of infants with a WAZ score of < -2 (P < 0.05). The infants with malnutrion in the high-calorie group had higher HAZ, WAZ, and WHZ than those in the conventional group (P < 0.05). No gastrointestinal intolerance was observed in both groups during hospitalization. CONCLUSIONS Compared with the standard formula, calorie-enriched formula can better help with postoperative catch-up growth in infants with cyanotic CHD.

Maternal Prenatal Cortisol and Breastfeeding Predict Infant Growth.

Fetal/infant growth affects adult obesity and morbidities/mortality and has been associated with prenatal exposure to cortisol. Bidirectional relations between maternal stress and breastfeeding suggest that they interact to influence offspring growth. No models have tested this hypothesis, particularly regarding longer-term offspring outcomes. We used a subset of the IDAHO Mom Study (n = 19–95) to examine associations among maternal prenatal cortisol (cortisol awakening response (CAR) and area under the curve), and standardized weight-for-length (WLZ) and length-for-age (LAZ) z-scores from birth-18 months, and main and interactive effects of prenatal cortisol and breastfeeding on infant growth from birth-6 months. CAR was negatively associated with LAZ at birth (r = −0.247, p = 0.039) but positively associated at 13–14 months (r = 0.378, p = 0.033), suggesting infant catch-up growth with lower birth weights, likely related to elevated cortisol exposure, continues beyond early infancy. A negative correlation between breastfeeding and 10-month WLZ (r = −0.344, p = 0.037) and LAZ (r = −0.468, p = 0.005) suggests that breastfeeding assists in managing infant growth. WLZ and LAZ increased from birth to 6 months (ps < 0.01), though this was unrelated to interactions between prenatal cortisol and breastfeeding (i.e., no significant moderation), suggesting that other factors played a role, which should be further investigated. Findings add to our understanding of the predictors of infant growth.

Customized versus population birth weight charts for identification of newborns at risk of long-term adverse cardio-metabolic and respiratory outcomes: a population-based prospective cohort study

BackgroundCustomized birth weight charts take into account physiological maternal characteristics that are known to influence fetal growth to differentiate between physiological and pathological abnormal size at birth. It is unknown whether customized birth weight charts better identify newborns at risk of long-term adverse outcomes than population birth weight charts. We aimed to examine whether birth weight classification according to customized charts is superior to population charts at identification of newborns at risk of adverse cardio-metabolic and respiratory health outcomes.MethodsIn a population-based prospective cohort study among 6052 pregnant women and their children, we measured infant catch-up growth, overweight, high blood pressure, hyperlipidemia, liver steatosis, clustering of cardio-metabolic risk factors, and asthma at age 10. Small size and large size for gestational age at birth was defined as birth weight in the lowest or highest decile, respectively, of population or customized charts. Association with birth weight classification was assessed using logistic regression models.ResultsOf the total of 605 newborns classified as small size for gestational age by population charts, 150 (24.8%) were reclassified as appropriate size for gestational age by customized charts, whereas of the total of 605 newborns classified as large size for gestational age by population charts, 129 (21.3%) cases were reclassified as appropriate size for gestational age by customized charts. Compared to newborns born appropriate size for gestational age, newborns born small size for gestational age according to customized charts had increased risks of infant catch-up growth (odds ratio (OR) 5.15 (95% confidence interval (CI) 4.22 to 6.29)), high blood pressure (OR 2.05 (95% CI 1.55 to 2.72)), and clustering of cardio-metabolic risk factors at 10 years (OR 1.66 (95% CI 1.18 to 2.34)). No associations were observed for overweight, hyperlipidemia, liver steatosis, or asthma. Newborns born large-size for gestational age according to customized charts had higher risk of catch-down-growth only (OR 3.84 (95% CI 3.22 to 4.59)). The direction and strength of the observed associations were largely similar when we used classification according to population charts.ConclusionsSmall-size-for-gestational-age newborns seem to be at risk of long-term adverse cardio-metabolic health outcomes, irrespective of the use of customized or population birth weight charts.

Umbilical Cord miRNAs in Small-for-Gestational-Age Children and Association With Catch-Up Growth: A Pilot Study.

Catch-up growth in infants who are small for gestational age (SGA) is a risk factor for the development of cardiometabolic diseases in adulthood. The basis and mechanisms underpinning catch-up growth in newborns who are SGA are unknown. To identify umbilical cord miRNAs associated with catch-up growth in infants who are SGA and study their relationship with offspring's cardiometabolic parameters. miRNA PCR panels were used to study the miRNA profile in umbilical cord tissue of five infants who were SGA with catch-up (SGA-CU), five without catch-up (SGA-nonCU), and five control infants [appropriate for gestational age (AGA)]. The miRNAs with the smallest nominal P values were validated in 64 infants (22 AGA, 18 SGA-nonCU, and 24 SGA-CU) and correlated with anthropometric parameters at 1 (n = 64) and 6 years of age (n = 30). miR-501-3p, miR-576-5p, miR-770-5p, and miR-876-3p had nominally significant associations with increased weight, height, weight catch-up, and height catch-up at 1 year, and miR-374b-3p, miR-548c-5p, and miR-576-5p had nominally significant associations with increased weight, height, waist, hip, and renal fat at 6 years. Multivariate analysis suggested miR-576-5p as a predictor of weight catch-up and height catch-up at 1 year, as well as weight, waist, and renal fat at 6 years. In silico studies suggested that miR-576-5p participates in the regulation of inflammatory, growth, and proliferation signaling pathways. Umbilical cord miRNAs could be novel biomarkers for the early identification of catch-up growth in infants who are SGA. miR-576-5p may contribute to the regulation of postnatal growth and influence the risk for cardiometabolic diseases associated with a mismatch between prenatal and postnatal weight gain.

Effects of oral zinc supplementation on zinc status and catch-up growth during the first 2 years of life in children with non-organic failure to thrive born preterm and at term

BackgroundWe aimed to analyze the effect of oral zinc supplementation on serum insulin-like growth factor-1 (IGF-1) levels and catch-up growth in infants with non-organic failure to thrive (NOFTT) who were born preterm as compared to those born at term. MethodsTotally, 105 NOFTT infants aged 2 years or less were enrolled and divided into two groups according to gestational age at birth. Oral zinc sulfate was administered for 6 months to 49/66 children born at term, and 21/39 children born preterm. Serum zinc, IGF-1, weight, and height were measured at baseline and at 6 months. ResultsThere were no differences in baseline serum zinc levels between the two groups. In preterm NOFTT infants, zinc supplementation significantly increased serum zinc levels compared to those in the non-supplementation group (Δ zinc 0–6 month 10.3 ± 26.4 μg/dL vs. −8.8 ± 23.7 μg/dL, p = 0.018), but it did not significantly change serum IGF-1 levels or weight- and height for age Z-scores. In NOFTT infants born at term who received zinc supplementation, serum zinc levels, IGF-1, weight for age Z-score, and height for age Z-score increased at 6 months (p = 0.001, p = 0.014, p = 0.049, and p = 0.029, respectively), but this increase was not significantly greater than in the non-supplementation group. Only the increase in serum zinc levels was significant after 6 months (Δ zinc 0–6 month 16.8 ± 32.0 μg/dL vs. −10.0 ± 22.6 μg/dL, p = 0.002). ConclusionZinc supplementation in NOFTT infants improves serum zinc status, regardless of gestational age at birth. Zinc supplementation in NOFTT infants born at term may improve serum IGF-1 levels and growth, but it does not in NOFTT infants born preterm. Overall nutritional support rather than supplementation of a single nutrient may be more effective for catch-up growth in NOFTT infants born preterm.

1103 Effective CPAP Treatment is Associated with Catch Up Growth in Infants with Obstructive Sleep Apnea and Failure to Thrive

1103 Effective CPAP Treatment is Associated with Catch Up Growth in Infants with Obstructive Sleep Apnea and Failure to Thrive

Evaluation of Neonatal Lung Volume Growth by Pulmonary Magnetic Resonance Imaging in Patients with Congenital Diaphragmatic Hernia

To evaluate postnatal lung volume in infants with congenital diaphragmatic hernia (CDH) and determine if a compensatory increase in lung volume occurs during the postnatal period. Using a novel pulmonary magnetic resonance imaging method for imaging neonatal lungs, the postnatal lung volumes in infants with CDH were determined and compared with prenatal lung volumes obtained via late gestation magnetic resonance imaging. Infants with left-sided CDH (2 mild, 9 moderate, and 1 severe) were evaluated. The total lung volume increased in all infants, with the contralateral lung increasing faster than the ipsilateral lung (mean ± SD: 4.9 ± 3.0 mL/week vs 3.4 ± 2.1 mL/week, P = .005). In contrast to prenatal studies, the volume of lungs of infants with more severe CDH grew faster than the lungs of infants with more mild CDH (Spearman's ρ=-0.086, P = .01). Although the contralateral lung volume grew faster in both mild and moderate groups, the majority of total lung volume growth in moderate CDH came from increased volume of the ipsilateral lung (42% of total lung volume increase in the moderate group vs 32% of total lung volume increase in the mild group, P = .09). Analysis of multiple clinical variables suggests that increased weight gain was associated with increased compensatory ipsilateral lung volume growth (ρ = 0.57, P = .05). These results suggest a potential for postnatal catch-up growth in infants with pulmonary hypoplasia and suggest that weight gain may increase the volume growth of the more severely affected lung.

A critical review: early life nutrition and prenatal programming for adult disease.

To present the evidence in relation to early life nutrition and foetal programming for adult disease. Epigenetics is a new and growing area of study investigating the impact of the intrauterine environment on the lifelong health of individuals. Discursive paper. Searches were conducted in a range of electronic health databases. Hand searches located additional articles for review. Maternal search terms included: pregnancy; nutrition; diet; obesity; over nutrition; under nutrition. Offspring related search terms included: macrosomia; intrauterine growth restriction; epigenetics; foetal programming; childhood obesity; adolescent obesity; adolescent type 2 diabetes. Results indicate that foetal programming for adult disease occurs in response to particular insults during vulnerable developmental periods. Four main areas of foetal exposure were identified in this review: (1) under nutrition; (2) over nutrition; (3) gestational diabetes mellitus; and (4) infant catch-up growth. Numerous studies also described the trans-generational nature of foetal programming. Overall, foetal exposure to excess or insufficient nutrition during vulnerable developmental periods appears to result in a lifelong predisposition to obesity and adult disease, such as type 2 diabetes and cardiac disease. For the infant who has been undernourished during early life, a predisposition to renal disease also occurs. Pregnancy is a time when women are engaged in health systems and are receptive to health messages. These factors suggest that pregnancy may be an optimal time for dietary education and intervention. There is a particular need for education on healthy diet and for interventions which aim to limit over consumption of calories.

Catch-up growth in infants with laryngomalacia after supraglottoplasty

ImportanceLaryngomalacia, the most common congenital anomaly of the infant airway, can lead to poor feeding and failure to thrive. The decision to perform the standard surgical treatment, supraglottoplasty, is often based upon a sustained period of poor weight gain or weight loss. ObjectiveTo characterize patterns of growth in infants with laryngomalacia, preceding and following supraglottoplasty. DesignRetrospective chart review. Bioinformatics techniques were used to procure data from a clinical data warehouse based on the HL7 Reference Information Model consisting of all infants who underwent supraglottoplasty from June 1, 2005 to October 31, 2013. Height and weight measurements were obtained from 76 operated patients allowing for characterization of growth changes from the time of surgery to an average of 9 months following surgery. Logistic regression analysis was performed to examine the following variables for correlations with changes in weight, height and body mass index percentiles: patient age at surgery, preoperative weight, gender, and ethnic background. SettingAcademic pediatric tertiary medical center. ParticipantsPatients under 2 years of age at the time of surgery, who underwent supraglottoplasty for laryngomalacia, with height and weight measurements recorded within 3 months preceding surgery and greater than 3 months following surgery. InterventionSupraglottoplasty. Main outcomes and measuresChange in weight, height and body mass index (BMI) percentile from pre-op to post-op. ResultsBMI increased from a mean of 15.4 to 18.0 and BMI percentile from a mean of 34 to 51 from pre-op to post-op. The largest BMI percentile increases were observed in infants that were 3 months or younger at the time of surgery, as well as in those under 12 months of age, who were in the lowest BMI quintile. Conclusions and relevanceInfants who underwent supraglottoplasty tended to be small in weight and stature, and gained weight after surgery. Most of the weight gain occurred within 6 months of surgery. The largest increases in BMI percentile were observed in infants who were younger and smaller at the time of surgery while the infants older than 18 months had no significant gain.

PS-297a Catch-up-growth In Term And Preterm Infants After Surgical Closure Of Ventricular Septal Defect In The First Year Of Life: Only Good News?

Failure to thrive is common in children with non-restrictive ventricular septal defect (VSD). Normalisation of growth has been reported after early surgical correction. However the literature is inconsistent about growth velocity after surgery in term and preterm infants. Objective Establishing the pattern of catch-up growth in infants submitted to VSD surgical repair before 1 year of age, for term and preterm infants. Methods 52 infants (41 term, 11 preterm) were studied. Anthropometric data at birth, at time of surgery and 3, 6, 12 and 24 months after surgery, collected retrospectively, were converted to z-scores. Statistic analyses was performed in SPSS® version 21, α=0,05. Results Mean weight and height z scores at the time of surgery were significantly lower for term infants (-2,24 and -1,42, respectively; p Conclusions Early surgical repair of VSD leads to a significant acceleration of growth, mainly in the first 3–6 months after surgery. An increased weight gain velocity has been associated with higher cardiovascular risk later in life. Knowledge of this specific catch-up growth pattern is important and should influence nutritional goals after surgery.

Preterm birth, infant weight gain, and childhood asthma risk: A meta-analysis of 147,000 European children

BackgroundPreterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results.ObjectivesWe performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years).MethodsFirst, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age <37 weeks) and low birth weight (<2500 g) with childhood asthma outcomes.ResultsYounger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27).ConclusionYounger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth.

Thrifty metabolic programming in rats is induced by both maternal undernutrition and postnatal leptin treatment, but masked in the presence of both: implications for models of developmental programming

BackgroundMaternal undernutrition leads to an increased risk of metabolic disorders in offspring including obesity and insulin resistance, thought to be due to a programmed thrifty phenotype which is inappropriate for a subsequent richer nutritional environment. In a rat model, both male and female offspring of undernourished mothers are programmed to become obese, however postnatal leptin treatment gives discordant results between males and females. Leptin treatment is able to rescue the adverse programming effects in the female offspring of undernourished mothers, but not in their male offspring. Additionally, in these rats, postnatal leptin treatment of offspring from normally-nourished mothers programmes their male offspring to develop obesity in later life, while there is no comparable effect in their female offspring.ResultsWe show by microarray analysis of the female liver transcriptome that both maternal undernutrition and postnatal leptin treatment independently induce a similar thrifty transcriptional programme affecting carbohydrate metabolism, amino acid metabolism and oxidative stress genes. Paradoxically, however, the combination of both stimuli restores a more normal transcriptional environment. This demonstrates that “leptin reversal” is a global phenomenon affecting all genes involved in fetal programming by maternal undernourishment and leptin treatment. The thrifty transcriptional programme was associated with pro-inflammatory markers and downregulation of adaptive immune mediators, particularly MHC class I genes, suggesting a deficit in antigen presentation in these offspring.ConclusionsWe propose a revised model of developmental programming reconciling the male and female observations, in which there are two competing programmes which collectively drive liver transcription. The first element is a thrifty metabolic phenotype induced by early life growth restriction independently of leptin levels. The second is a homeostatic set point calibrated in response to postnatal leptin surge, which is able to over-ride the metabolic programme. This “calibration model” for the postnatal leptin surge, if applicable in humans, may have implications for understanding responses to catch-up growth in infants. Additionally, the identification of an antigen presentation deficit associated with metabolic thriftiness may relate to a previously observed correlation between birth season (a proxy for gestational undernutrition) and infectious disease mortality in rural African communities.

Developmental Origins of Obesity: Programmed Adipogenesis

The metabolic syndrome epidemic, including a marked increase in the prevalence of obesity and gestational diabetes mellitus (GDM) among pregnant women, represents a significant public health problem. There is increasing recognition that the risk of adult obesity is clearly influenced by prenatal and infant environmental exposures, particularly nutrition. This tenet is the fundamental basis of developmental programming. Low birth weight, together with infant catch-up growth, is associated with a significant risk of adult obesity. Exposure to maternal obesity, with or without GDM, or having a high birth weight also represents an increased risk for childhood and adult obesity. Animal models have replicated human epidemiologic findings and elucidated potential programming mechanisms that include altered organ development, cellular signaling responses, and epigenetic modifications. Prenatal care has made great strides in optimizing maternal, fetal, and neonatal health, and now has the opportunity to begin interventions which prevent or reduce childhood/adult obesity. Guidelines that integrate optimal pregnancy nutrition and weight gain, management of GDM, and newborn feeding strategies with long-term consequences on adult obesity, remain to be elucidated.

Urinary osteocalcin and serum pro-C-type natriuretic peptide predict linear catch-up growth in infants

Preterm (PT) infants are at risk of growth failure despite advanced early care and nutrition. In addition to poor weight gain, slow postnatal linear growth also is associated with adverse neurological outcome. Markers distinguishing infants at risk for impaired catch-up growth are needed. The aim of this longitudinal study was to determine the extent to which postnatal levels of circulating cartilage (serum pro-C-type natriuretic peptide [S-proCNP]) and urinary bone metabolic markers (urinary osteocalcin [MidOC] and two forms of C-terminal cross-linked telopeptide of type I collagen [U-α-CTX-I and U-β-CTX-I]) predict catch-up growth in infancy in 67 PT and 58 full-term (FT) infants. PT infants were significantly shorter than FT infants during the first 6 months of life, but no statistically significant difference was found at the corrected age of 14 months (M14). At the age of 3 months (M3), S-ProCNP and U-MidOC levels, but not U-α-CTX-I and U-β-CTX-I levels, correlated positively with prospective growth velocity from M3 to M14 (ρ = 0.460, p < 0.001 and ρ = 0.710, p < 0.001, respectively). In predicting slow linear growth (growth velocity at the lowest quartile), the area under the S-ProCNP ROC curve was 0.662 and that of U-MidOC 0.891. Thus, U-MidOC, and to lesser extent S-ProCNP at M3 are predictors of catch-up growth in infancy.