Growth of pediatric recipients after renal transplantation from small pediatric deceased donors weighing less than 15 kg

RTx is currently the best treatment for children with ESRD. This study retrospectively analyzed the outcomes of growth after RTx using the pediatric‐to‐pediatric allocation strategy and some factors that may affect it. From March 2012 to August 2016, 8 en bloc and 38 single pediatric RTxs were performed at our center using organs from small pediatric deceased donors (weight < 15 kg). Growth before and after RTx was analyzed according to the height‐for‐age z‐score at RTx, the 3‐year follow‐up, and adulthood and compared between the procedures. The chi‐square test and multiple linear regression analysis were used for statistical analyses. Overall, 79.2% of children were diagnosed with chronic nephritis before RTx; 14.6% of cases were due to congenital urinary tract malformation, and 6.3% of cases were due to unknown causes. All grafts and patients survived postoperatively. The mean estimated GFRs were 92.7 ± 28.6 mL/min/1.73 m², 100.9 ± 32.3 mL/min/1.73 m², and 110.1 ± 34.8 mL/min/1.73 m² at 1, 2, and 3 years’ postoperatively, respectively. The children's postoperative growth and development, particularly during the first year postoperatively, improved but were negatively correlated with age and the height‐for‐age z‐score before RTx. The growth of children after RTx was moderate and accelerated during prepubescence. The rate of post‐RTx growth during the first year postoperatively was unrelated to the recipient's sex or duration of dialysis (P > 0.05) but was negatively correlated with age at RTx (r = ?0.349, P = 0.043). Future studies on the long‐term outcomes are still needed.     

Seropositivity to celiac antigens in asymptomatic children with type 1 diabetes mellitus: association with weight, height, and bone mineralization

Background:  Screening for celiac disease (CD) in children with diabetes is controversial because no studies have demonstrated metabolic complications in asymptomatic, seropositive subjects or beneficial effects of dietary intervention.
Objective:  We hypothesized that seropositivity to celiac antigens is associated with decreased growth and bone mineralization in asymptomatic diabetic children.
Design/Methods:  Asymptomatic diabetic children were screened for seropositivity to tissue transglutaminase. Villous atrophy was assessed by small bowel biopsy in a subset of seropositive subjects. We compared measures of growth and bone mineralization in 30 seropositive subjects, and 34 matched seronegative controls.
Results:  Relative to seronegative controls, the seropositive subjects had reductions in insulin-like growth factor (IGF) binding protein 3 z scores (p < 0.05) and bone mineral density (BMD) z scores (p = 0.05). Weight, body mass index, IGF-I, and bone mineral apparent density (BMAD) z scores were marginally lower, but height z scores were comparable. Seropositive patients with severe villous atrophy had lower weight (−0.91 SDs), height (−1.1 SDs), BMD (−2.0 SDs), and BMAD (−2.0 SDs) z scores and significant increases in parathyroid hormone (all p < 0.05). Four patients with severe villous atrophy maintained strict gluten restriction for at least 12 months. Gluten restriction increased BMD and BMAD z scores.
Conclusions:  High-titer seropositivity to celiac antigens is associated with reductions in weight and BMD in diabetic children, justifying screening of high-risk patients. Results suggest that biopsy is required to confirm the diagnosis and assess the severity of CD; those with severe villous atrophy are more likely to have growth failure and osteopenia. Gluten restriction may reverse these complications.     

Efficacy of prophylactic additional cranial irradiation and intrathecal chemotherapy for the prevention of CNS relapse after allogeneic hematopoietic SCT for childhood ALL

We evaluated the efficacy of CRT and IT chemotherapy, in addition to conditioning including TBI, for the prevention of CNS relapse, in allogeneic HSCT for childhood ALL. From January 1999 to December 2009, a total of 48 patients, without previous or presenting CNS involvement, underwent HSCT for ALL. All patients received myeloablative conditioning including TBI of 12 or 13.2 Gy and IT chemotherapy twice between days ?10 and ?2 prior to HSCT. Twenty‐five patients received CRT prior to TBI (CRT+), and 23 patients did not (CRT?). CRT+ and CRT? patients had a seven‐yr EFS rate of 40.0 ± 9.8% and 41.7 ± 10.6%, respectively (p = 0.8252). The seven‐yr relapse rates for CRT+ and CRT? patients were 45.0 ± 11.2% and 38.4 ± 11.6%, respectively (p = 0.7460). CNS relapses were evident in 1 (4.0%) CRT+ patient and 1 (4.4%) CRT? patient (p = 1.000). There were no significant differences in EFS and the probability of CNS relapse between CRT+ and CRT? patients. These results demonstrate that CRT and IT chemotherapy, in addition to conditioning chemotherapy, may not be necessary in childhood ALL patients without previous or presenting CNS involvement.     

Clinical comparison of weight‐ and age‐based strategy of dose administration in children receiving intravenous busulfan for hematopoietic stem cell transplantation

Bu, combined with TDM‐guided dosing, is associated with fewer graft failures/relapses and lower toxicity in pediatric HSCT. We aimed this retrospective study for comparison of weight‐ and age‐based dosing in terms of clinical outcomes such as time to engraftment, early complications, EFS, OS, and toxicity profiles in children receiving iv Bu. Sixty‐one children who underwent HSCT from April 2010 to February 2013 by means of a Bu‐based conditioning regimen and completed 100 days after transplantation at Ankara Children?s Hematology and Oncology Hospital Bone Marrow Transplantation Unit were enrolled in this study. SOS and neutropenic fever occurred more frequently in the weight‐based dosing group. We found a statistically significant correlation between Bu dose and the incidence of SOS (r = 0.26, p = 0.04). Multivariate analysis showed only weight‐based dosing of Bu was a significant predictor of SOS (HR = 9.46; p = 0.009). However, no relationship was found between two groups in terms of hemorrhagic cystitis, engraftment syndrome, acute or chronic GvHD, time to engraftment, chimerism, TRM, OS, and EFS rates. Weight‐based dosing of Bu may cause higher incidence of SOS and early infectious complications at the places where TDM of Bu cannot be performed.     

Relationships between OPG,RANKL, bone metabolism,and bone mineral density in biliary atresia

Purpose  Osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) have been implicated in osteoclastogenesis. However, the relationship between the OPG–RANKL system and bone status in biliary atresia (BA) has not, as yet, been clarified. Thus, the aim of this study has been to evaluate the relationship between the OPG–RANKL system and bone mineral metabolism in patients with BA. Methods  Fifty patients with BA and 13 healthy controls were investigated. The mean age of BA patients and controls was 7.3 ± 0.6 and 8.0 ± 1.1 years, respectively. Serum levels of OPG, RANKL, osteocalcin, and C-terminal telopeptide of type I collagen (CTX) were measured by sandwich enzyme-linked immunosorbent assay. Bone mineral density (BMD) of the lumbar spine was determined by dual energy X-ray absorptiometry. Results  Biliary atresia patients had significantly elevated serum OPG levels compared with controls (4.0 ± 0.3 vs. 3.0 ± 0.3 pmol/L, P = 0.02) and serum OPG levels in BA patients with jaundice were higher than in those without jaundice (4.6 ± 0.4 vs. 3.6 ± 0.4 pmol/L, P = 0.04). Likewise, serum RANKL levels were significantly higher in BA patients than in controls (2.9 ± 0.2 vs. 1.2 ± 0.7 pmol/L, P = 0.001). In addition, serum RANKL levels were increased in BA patients with jaundice compared to those without jaundice, but this difference was not statistically significant (3.2 ± 0.3 vs. 2.7 ± 0.2 pmol/L, P = 0.2). The serum osteocalcin levels in BA patients were not significantly different from those in the healthy controls, whereas the serum CTX levels were elevated in BA patients compared with the controls (0.4 ± 0.1 vs. 0.2 ± 0.1 ng/mL, P = 0.02). Furthermore, BMD of BA children with jaundice was significantly lower than that of BA children without jaundice (P = 0.0005). BMD of BA patients was inversely correlated with serum levels of OPG (r = −0.452, P < 0.001). Conclusion  Elevated serum OPG levels are associated with reduced BMD and the outcome of BA. The increase of serum OPG in BA patients with severe disease could reflect a compensatory response to bone loss. Presented at the 30th American Society for Bone and Mineral Research (ASBMR) annual meeting, Montreal, Quebec, Canada, 12–16 September 2008.     

Maternal plasma cholesterol and duration of pregnancy: A prospective cohort study in Ghana

Low plasma cholesterol may be associated with preterm birth; however, results are mixed and limited primarily to high‐income countries. Our objective was to determine whether maternal plasma lipid concentrations are associated with pregnancy duration. We performed a nested cohort (n = 320) study of pregnant Ghanaian women enrolled in a randomized controlled trial. Total cholesterol, high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol, and triglyceride concentrations were analyzed in plasma at ≤20and 36 weeks gestation as continuous variables and also categorized into low, referent, or high (<10th, 10th–90th, >90th percentile). At ≤20 weeks, plasma lipid concentrations were not associated with pregnancy duration. At 36 weeks, total cholesterol and triglyceride concentrations were not associated with pregnancy duration. Higher HDL‐C at 36 weeks was associated with a longer pregnancy duration (adjusted β‐coefficient ± standard error: 0.05 ± 0.02 days mg^?1/dL, p = .02); pregnancy duration was 5.9 ± 2.0 (mean ± standard error) days shorter among women with low HDL‐C compared with the referent group (10th–90th percentile) (p = .02) and 8.6 ± 2.6 days shorter when compared with the high HDL‐C group (p = .003). Pregnancy duration was 4.9 ± 2.1 days longer among women with low low‐density lipoprotein cholesterol at 36 weeks gestation when compared with the referent group (p = .051). Our data suggest that low HDL‐C in the third trimester of pregnancy is associated with a shorter duration of pregnancy in this study population but do not support the hypothesis that low total cholesterol is associated with a shorter pregnancy duration.     

Cardiometabolic correlates of sleep‐disordered breathing in renal transplant children

Sleep‐disordered breathing, a prevalent condition among adult renal transplant (RTx) recipients, has become an established independent risk factor of MetS, and furthermore, it might contribute to increased CV risk. Despite the proven correlations in adults, there is a lack of evidence for its significance in the pediatric RTx population. In this study, we aimed at assessing the prevalence and the clinical correlates of SDB in RTx children. Data of 13 patients (age [mean ± SD]: 14.2 ± 2.7 years) were analyzed. SDB was evaluated by PSG, as severity score OAHI was applied. Carbohydrate metabolism was characterized by OGTT, whereas CV status was studied by ABPM. Three composite end‐points were calculated as sum of z‐scores: daytime systolic and diastolic BP; nighttime systolic and diastolic BP; and glucose and insulin levels at 120 minutes. Eight patients (61.5%) were diagnosed with SDB of whom five patients (38.5%) had moderate or severe SDB. In linear regression analysis, OAHI during REM was associated with the CV variables (daytime BP P = 0.032, ß = 0.748; nighttime BP P = 0.041, ß = 0.715), and the correlations remained significant after adjustments for BMI. However, we did not confirm a significant association with the metabolic variables. The prevalence of SDB was high, and its severity during REM was a predictor of the BP suggesting that RTx children with SDB might be at risk of developing CV complications, especially HTN similarly to adults.     

Decline in ventricular function as a result of general anesthesia in pediatric heart transplant recipients

Echocardiography is frequently performed under anesthesia during procedures such as cardiac catheterization with EMB in pediatric HTx recipients. Anesthetic agents may depress ventricular function, resulting in concern for rejection. The aim of this study was to compare ventricular function as measured by echocardiography before and during GA in 17 pediatric HTx recipients. Nearly all markers of ventricular systolic function were significantly decreased under GA, including EF (?4.2% ±1.2, P < .01) and RV FAC (?0.05 ± 0.02, P = .04). Subjects in the first post‐transplant year (n = 9) trended toward a more significant decrease in EF vs those beyond the first post‐transplant year (n = 8; ?6.0% ±1.2 vs ?2.1 ± 2.0, P = .1). This information quantifies a decline in biventricular function that should be expected in pediatric HTx recipients while under GA and can assist the transplant clinician in avoiding unnecessary treatment of transient GA‐induced ventricular dysfunction.     

Bone mass density and associated factors in cystic fibrosis patients of young age

Aim: To investigate bone mineral status in young cystic fibrosis (CF) patients and determine risk factors related with the development of low bone mineral density (BMD). Methods: We determined, in 81 patients with CF, 4 to 23‐years‐old, BMD as well as factors, which are thought to play a role in the development of reduced BMD. Results: BMD Z‐score was between ?1 and ?2.5 in 27 (33%) and lower than ?2.5 in 9 (11%). Means of BMD Z‐score were lower than the expected value of 0 in the three groups of children, adolescents and young adults (P = 0.004; P < 0.001; P = 0.048, respectively), but they did not differ among them (P = 0.114). Analysis showed that Shwachman–Kulczycki (SK) score, gender and levels of 25‐hydroxy‐vitamin D were significant predictors of BMD Z‐score. Significant also was the interaction between gender and SK score. Conclusions: Our study supports that BMD may be reduced from a young age in CF patients though this needs to be confirmed using true volumetric measures of BMD. This defect is related to disease severity with males being more vulnerable. Inefficient levels of vitamin D are very common and contribute significantly to impaired bone health. The latter finding underlines the need for higher supplementation doses.     

Changes in cardiac function after renal transplantation in children: Significance of pre‐transplantation left ventricular hypertrophy

LVH is a significant risk factor for the development of cardiovascular morbidity. However, few studies have evaluated the changes in cardiac function that occur in pediatric patients with ESRD undergoing RTx. Therefore, we assessed the changes in parameters associated with LVH in children within the first year after RTx. We retrospectively evaluated patients aged < 18 years who underwent initial RTx from April 2014 to December 2016. The patients were divided into 2 groups according to the presence of LVH before RTx. Clinical, biochemical, and echocardiographic parameters including the LVMI before and 1 year after RTx were evaluated in both groups. Twenty‐six patients were included in this study. Seven of the 26 patients had LVH before RTx. Among the echocardiographic parameters, the LVMI was significantly improved 1 year after RTx in the initial LVH group (57.79 ± 11.86 vs 42.20 ± 6.03 g/cm^2.7, P = .018), while no change was observed in the initial non‐LVH group (32.66 ± 7.52 vs 35.17 ± 12.86 g/cm^2.7, P = .376). Improvement of the ejection fraction was also observed only in the initial LVH group (66.5% ± 5.3% vs 72.2% ± 5.2%, P = .042). Children who had LVH before RTx showed significant improvements in the LVMI and ejection fraction even within 1 year after RTx. To minimize aggravation of cardiac function, early RTx should be considered for patients with LVH.     

B‐type natriuretic peptide trends after pediatric heart transplantation

BNP is increasingly utilized in the management of pediatric HT recipients. Performing a retrospective single‐center chart review, we sought to describe BNP changes during the first year after HT and identify factors that affect its trend. After exclusion for rejection, 316 BNP levels from 50 patients were evaluated. BNP underwent an exponential decline 120 days after HT followed by a plateau. Log₁₀BNP decline strongly correlated with time (r = ?0.70, p < 0.0001). Initial BNP was less in pretransplant VAD (p = 0.0016) and lower post‐HT inotrope use (p = 0.0043). Infant recipients, IT >4 h, and those bridged medically were associated with higher plateau BNP. Multivariable logistic regression demonstrated IT >4 h independently predicted plateau BNP in the upper quartile (OR 7.1, p = 0.02). No significant change in BNP coincided with rejection (N = 6 patients) without severe hemodynamic compromise. BNP correlated modestly with right atrial pressure (r = 0.4652, p < 0.0001) and pulmonary capillary wedge pressure (r = 0.2660, p < 0.001), but poorly with echocardiogram (r = ?0.18, p = 0.003). Trending BNP could help provide insight into how the graft recovers after HT and IT >4 h independently predicted higher plateau BNP and may reflect subtle changes in graft performance.     

Prevalence of abnormal bone density of pediatric patients prior to blood or marrow transplant

Osteoporosis and osteopenia are long‐term side effects of bone marrow transplant (BMT). The purpose of this study was to determine the prevalence of bone mineral density (BMD) abnormalities in pediatric patients prior to BMT. Forty‐four pediatric patients were evaluated with DEXA scans. The average Z‐score was ?0.37. Thirty‐six percent had abnormal BMD. Sixty‐seven percent of ALL patients had abnormal BMD. Patients with non‐malignant diseases were significantly more likely to have abnormal BMD. Patients with ALL had more defects than solid tumor patients. Females had more defects than males. These results demonstrate BMD defects are common in children prior to BMT, especially in patients with ALL. Pediatr Blood Cancer 2009;53:675–677. © 2009 Wiley‐Liss, Inc.     

Physical activity and health related quality of life in children following kidney transplantation

Abstract:  Participation in PA is often diminished in children with CKD. Limited research exists on exercise tolerance/capacity but no studies to date have investigated lifestyle PA and its determinants in these children. The aim of this study was to investigate level of PA and potential physiological and psychological associations in a group of pediatric KTx recipients compared with CS. Twenty KTx and 33 CS participated. PA was measured by PAQ. HRQOL (PedsQL 4.0) and CY-PSPP were also measured. BMI and WC was recorded in all subjects; GFR, BP and immunosuppressants in KTx. Body measurements indicated the two groups were similar: 25% KTx and 24% CS had BMI >85th percentile. KTx were less physically active than CS in total exercise minutes (p = 0.005). CS reported higher HRQOL than KTx (p = 0.001). Higher perceptions of HRQOL were significantly correlated with higher number of steps/day in both groups (p = 0.034). KTx showed significantly lower perceptions of sports competence (p = 0.007) and physical conditioning (p = 0.001) than CS. Higher PAQ activity scores were significantly correlated with higher perceptions of body attractiveness (p = 0.019), Sport (p = 0.003) and Conditioning (p = 0.001). These results suggest that PA may play a role in overall well-being and HRQOL in KTx.     

Bone mineral status in pediatric heart transplant recipients: A retrospective observational study of an “at risk” cohort

Sachdeva R, Soora R, Bryant JC, Seibert JJ, Blaszak RT, Frazier EA. Bone mineral status in pediatric heart transplant recipients: A retrospective observational study of an “at risk” cohort.
Pediatr Transplantation 2010:14: 383–387. © 2009 John Wiley & Sons A/S. Abstract: There is a paucity of literature assessing the burden of bone loss in PHT recipients. We sought to describe the bone mineral status in PHT recipients by doing a retrospective medical record review of those who underwent evaluation of BMD when clinically indicated. Data collected included patient demographics, BMD evaluations, serum calcium, phosphorus, alkaline phosphatase, cumulative steroid dose, osseous complications and their management. Of 149 PHT recipients, 26 underwent BMD evaluation. This evaluation was done at a median of 3.4 yrs after PHT. There total serum calcium, phosphorus and alkaline phosphatase were similar at transplant and BMD study. The median BMD Z‐scores were: whole body ?0.09 (1.5 to ?5.13) and lumbar spine ?1.1 (1.5 to ?5.16). Bone loss (Z‐score 相似文献   

Two‐year follow‐up of a postpartum weight loss intervention: Results from a randomized controlled trial

We recently reported that a 12‐week diet intervention among postpartum women produced a weight loss of 12% after 1 year, compared to 5% in controls. Here, we present 2‐year results after 1 year of unsupervised follow‐up. In total, 110 women with a self‐reported body mass index of ≥27 kg/m² at 6–15‐week postpartum were randomized to diet group (D‐group) or control group (C‐group). D‐group received a 12‐week diet intervention by a dietitian followed by monthly e‐mails up to the 1‐year follow‐up. C‐group received a brochure on healthy eating. No contact was provided from 1 to 2 years to either group. Eighty‐nine women (81%) completed the 2‐year follow‐up. Median (1st; 3rd quartile) weight change from 0 to 2 years was ?6.9 (?11.0; ?2.2) kg in D‐group and ?4.3 (?8.7; ?0.2) kg in C‐group. There was no group by time interaction at 2 years (p = .082); however, when women with a new pregnancy between 1 and 2 years were excluded, the interaction became significant (?8.2 vs. ?4.6 kg, p = .038). From 1 to 2 years, women in D‐ and C‐group gained 2.5 ± 5.0 kg and 1.1 ± 4.4 kg, respectively (p = .186). Women who gained weight from 1 to 2 years reported a decrease in self‐weighing frequency compared to women who maintained or lost weight (p = .008). Both groups achieved clinically relevant 2‐year weight loss, but the significant between‐group‐difference observed at 1 year was not maintained at 2 years in the main analysis. However, when women with a new pregnancy between 1 and 2 years were excluded, a significant weight loss effect was observed also at 2 years.     

Transition from brand to generic tacrolimus is associated with a decrease in trough blood concentration in pediatric heart transplant recipients

There are limited data available on the bioequivalence of generic and brand‐name tacrolimus in pediatric and heart transplant patients. We characterized changes in 12‐hour trough concentrations and clinical outcomes after transition from brand to generic tacrolimus in pediatric thoracic organ transplant recipients. Patients with a pharmacy‐confirmed date of switch between generic and brand tacrolimus were identified, as well as a matched control group that did not switch for comparison. We identified 18 patients with a confirmed date of switch, and in 12 patients that remained on the same dose, trough concentrations were 14% less than when they were on brand (p = 0.037). The average change was ?1.15 ± 1.76 ng/mL (p = 0.045). The control group did not experience a change in trough concentration and was different than the switched group (p = 0.005). There were no differences in dosage changes or kidney or liver function. In the year after switch, 24% of patients who were switched to generic experienced a rejection event vs. 18% in the patients on brand. We suggest a strategy of monitoring around the time of transition, and education of the patient/family to notify the care team when changes from brand to generic or between generics occur.     

Strain and strain rate imaging using speckle tracking in acute allograft rejection in children with heart transplantation

Acute allograft rejection is a major cause of morbidity and mortality following heart transplantation. There is no reliable noninvasive test to diagnose rejection. We aimed to investigate the accuracy of strain by speckle tracking echocardiography in the detection of acute rejection. We identified acute rejection episodes in patients followed at a single transplant center. Data were collected at baseline, during rejection and two follow‐up points. Peak systolic radial and circumferential strain at the level of papillary muscles and peak systolic longitudinal strain from apical four‐chamber view were analyzed offline. ANOVA was used for comparison between groups. p value ≤0.05 was considered significant. Fifteen rejection episodes were identified. There were no differences in the fractional shortening, LV posterior wall thickness, E/A, septal E/E’, septal S’, lateral E/E’, lateral S’, or MPI during rejection, compared to baseline. There was a significant increase in the LV mass during a rejection episode (47.5 vs. 34.4 g/ht^2.7 [p = 0.03]). The peak systolic radial strain (18.3 vs. 26.5; p = 0.03), longitudinal strain (?11.7 vs. ?14.6; p = 0.05), and circumferential strain (?14.4 vs. ?21.7; p = 0.05) declined significantly during rejection. In conclusion, peak systolic radial, longitudinal and circumferential strain decline and LV mass increases during an episode of rejection.     

Quantitative ultrasonometry of the calcaneus in children with osteogenesis imperfecta

Aims: Osteogenesis imperfecta (OI) is characterised by low bone density and increased bone fragility. The aim was to evaluate calcaneal quantitative ultrasonometry (QUS) parameters in children with OI and to look for relationship with the number of prevalent fractures. Methods: Eighteen children (12 boys and six girls; mean age 9.8 ± 3.5 years) with OI (type I, n= 15; type IV, n= 3; mean fracture prevalence 3.7 per patient) had the velocity of sound (VOS) and broadband ultrasound attenuation (BUA) measured on both heels with a Cuba Clinical (McCue Ultrasonics, Winchester, UK) dry ultrasound portable device. Both BUA and VOS were expressed as either age‐dependent or height‐related values. The obtained values of VOS and BUA were correlated to number of prevalent fractures. Results: The patients were of short stature (Z‐score –1.73 ± 1.20 SD; P < 0.001). Both age‐related BUA and VOS were low in comparison to reference values (P < 0.0001), same as height‐adjusted BUA and VOS (P < 0.0001). We found no correlations between number of prevalent fractures and BUA or VOS (age‐related or height‐adjusted) (r= 0.02, r= 0.017, r=–0.13, r= 0.015, respectively). Conclusions: Children with OI have low QUS parameters with no relationship to number of prevalent fractures.     

Epigenetic modulation at birth – altered DNA-methylation in white blood cells after Caesarean section

Aim:  Delivery by C-section (CS) has been associated with increased risk for allergy, diabetes and leukaemia. Whereas the underlying cause is unknown, epigenetic change of the genome has been suggested as a candidate molecular mechanism for perinatal contributions to later disease risk. We hypothesized that mode of delivery affects epigenetic activity in newborn infants.
Methods:  A total of 37 newborn infants were included. Spontaneous vaginal delivery (VD) occurred in 21, and 16 infants were delivered by elective CS. Blood was sampled from the umbilical cord and 3–5 days after birth. DNA-methylation was analyzed in leucocytes.
Results:  Infants born by CS exhibited higher DNA-methylation in leucocytes compared with that of those born by VD (p < 0.001). After VD, newborn infants exhibited stable levels of DNA-methylation, as evidenced by comparing cord blood values with those 3–5 days after birth (p = 0.55). On postnatal days 3–5, DNA-methylation had decreased in the CS group (p = 0.01) and was no longer significantly different from that of VD (p = 0.10).
Conclusion:  DNA-methylation is higher in infants delivered by CS than in infants vaginally born. Although currently unknown how gene expression is affected, or whether epigenetic differences related to mode of delivery are long-lasting, our findings open a new area of clinical research with potentially important public health implications.