Development of a Pipeline for Exploratory Metabolic Profiling of Infant Urine.

Numerous metabolic profiling pipelines have been developed to characterize the composition of human biofluids and tissues, the vast majority of these being for studies in adults. To accommodate limited sample volume and to take into account the compositional differences between adult and infant biofluids, we developed and optimized sample handling and analytical procedures for studying urine from newborns. A robust pipeline for metabolic profiling using NMR spectroscopy was established, encompassing sample collection, preparation, spectroscopic measurement, and computational analysis. Longitudinal samples were collected from five infants from birth until 14 months of age. Methods of extraction and effects of freezing and sample dilution were assessed, and urinary contaminants from breakdown of polymers in a range of diapers and cotton wool balls were identified and compared, including propylene glycol, acrylic acid, and tert-butanol. Finally, assessment of urinary profiles obtained over the first few weeks of life revealed a dramatic change in composition, with concentrations of phenols, amino acids, and betaine altering systematically over the first few months of life. Therefore, neonatal samples require more stringent standardization of experimental design, sample handling, and analysis compared to that of adult samples to accommodate the variability and limited sample volume.

Multiplatform characterization of dynamic changes in breast milk during lactation.

The multicomponent analysis of human breast milk (BM) by metabolic profiling is a new area of study applied to determining milk composition, and is capable of associating BM composition with maternal characteristics, and subsequent infant health outcomes. A multiplatform approach combining HPLC-MS and ultra-performance LC-MS, GC-MS, CE-MS, and 1 H NMR spectroscopy was used to comprehensively characterize metabolic profiles from seventy BM samples. A total of 710 metabolites spanning multiple molecular classes were defined. The utility of the individual and combined analytical platforms was explored in relation to numbers of metabolites identified, as well as the reproducibility of the methods. The greatest number of metabolites was identified by the single phase HPLC-MS method, while CE-MS uniquely profiled amino acids in detail and NMR was the most reproducible, whereas GC-MS targeted volatile compounds and short chain fatty acids. Dynamic changes in BM composition were characterized over the first 3 months of lactation. Metabolites identified as altering in abundance over lactation included fucose, di- and triacylglycerols, and short chain fatty acids, known to be important for infant immunological, neurological, and gastrointestinal development, as well as being an important source of energy. This extensive metabolic coverage of the dynamic BM metabolome provides a baseline for investigating the impact of maternal characteristics, as well as establishing the impact of environmental and dietary factors on the composition of BM, with a focus on the downstream health consequences this may have for infants.

Aberrant adiposity and ectopic lipid deposition characterize the adult phenotype of the preterm infant.

Our investigation addresses the hypothesis that disruption of third trimester development by preterm birth alters multiple biological pathways affecting metabolic health in adult life. We compared healthy adult volunteers aged 18-27 y born at ≤ 33 wk gestation or at term. We used whole-body MRI, (1)H magnetic resonance spectroscopy (MRS) of liver and muscle, metabonomic profiling of blood and urine, and anthropometric and blood pressure measurements. Preterm subjects had greater (mean difference (95% CI)) total [2.21 L (0.3, 4.1), p = 0.03] and abdominal adipose tissue [internal 0.51 (0.1, 0.9), p = 0.007]; blood pressure [systolic 6.5 mm Hg (2.2, 10.8), p = 0.004; diastolic 5.9 (1.8, 10.1), p = 0.006]; and ectopic lipid (ratio (95% CI)), intrahepatocellular lipid (IHCL) 3.01 (1.78, 5.28) p < 0.001, and tibialis-intramyocellular lipid (T-IMCL) [1.31 (1.02, 1.69) p = 0.04]. In preterm, compared with term men, there was greater internal adipose tissue [mean (SD); men: preterm 4.0 (1.6), term 2.7 (1.1) liters; women: preterm 2.6 (0.9); term 2.6 (0.5); gender-gestation interaction p = 0.048] and significant differences in the urinary metabolome (elevated methylamines and acetyl-glycoproteins, lower hippurate). We have identified multiple premorbid biomarkers in ex-preterm young adults, which are most marked in men and indicative of risks to later wellbeing. These data offer insight into biological trajectories affected by preterm birth and/or neonatal care.

The influence of maternal body mass index on infant adiposity and hepatic lipid content.

Maternal overweight and obesity are associated with adverse offspring outcome in later life. The causal biological effectors are uncertain. Postulating that initiating events may be alterations to infant body composition established in utero, we tested the hypothesis that neonatal adipose tissue (AT) content and distribution and liver lipid are influenced by maternal BMI. We studied 105 healthy mother-neonate pairs. We assessed infant AT compartments by whole body MR imaging and intrahepatocellular lipid content by H MR spectroscopy. Maternal BMI ranged from 16.7 to 36.0. With each unit increase in maternal BMI, having adjusted for infant sex and weight, there was an increase in infant total (8 mL; 95% CI, 0.09-14.0; p = 0.03), abdominal (2 mL; 95% CI, 0.7-4.0; p = 0.005), and nonabdominal (5 mL; 95% CI, 0.09-11.0; p = 0.054) AT, and having adjusted for infant sex and postnatal age, an increase of 8.6% (95% CI, 1.1-16.8; p = 0.03) in intrahepatocellular lipid. Infant abdominal AT and liver lipid increase with increasing maternal BMI across the normal range. These effects may be the initiating determinants of a life-long trajectory leading to adverse metabolic health.

Delivery by Caesarean section, rather than vaginal delivery, promotes hepatic steatosis in piglets.

There has been a marked increase in the number of babies born by elective CS (Caesarean section). Following CS, the lack of normal stimuli that occur at birth alters the thermogeneic response, but any effects on hepatic metabolism have not been identified. In the present study, we compared the effect of delivery on hepatic metabolism in piglets, born either by CS or VD (vaginal delivery) and fed by TPN (total parenteral nutrition), by measuring lipid metabolism and enzyme activity coupled with metabolomic and genomic approaches. Hepatic lipid in the CS piglets at 7 days post-partum was in excess of 5 mg/g of liver consistent with hepatic steatosis, whereas in the VD piglets the amount of lipid was markedly lower (3 mg/g of liver) and below the threshold for a diagnosis of steatosis. Metabolomic analysis indicated that CS resulted in higher hepatic glycerol and lower glycerol phosphate dehydrogenase activity, suggesting that CS causes a decrease in hepatic gluconeogenesis from glycerol. CS also resulted in altered cholesterol handling and gene expression, despite the same dietary intake for 7 days post-partum. Furthermore, the CS piglets had a lower expression of interferon-responsive genes, but a higher expression of markers of immature hepatocytes. In conclusion, the results suggest that VD promotes normal liver maturation and hepatic metabolism, thereby reducing the accumulation of hepatic lipid.

Preceptors' Perception of Role Competency.

BACKGROUND: Many variables contribute to the success of nursing students and new nurses in their transition to practice. Clinical orientation and training usually falls to staff nurse preceptors. Inherent in this dynamic is the assumption that staff nurses are prepared and able to assume this responsibility. Ideal characteristics and attributes of preceptor competency have not been conclusively defined. METHOD: This qualitative study explored the defining attributes of preceptor role competency as described by preceptors who attended one of 44 continuing education preceptor academies over 9 years in Missouri. RESULTS: Analysis revealed that communication, expertise, flexibility, evaluation skills, and patience are among the most important competencies of nurse preceptors. CONCLUSION: Understanding role expectations would benefit both preceptors and nurse educators who select, train, and support nurse preceptors. Identification of essential preceptor competencies can inform preceptor preparation courses and identify needs for continuing education of preceptors. J Contin Educ Nurs. 2018;49(5):233-240.

Review of State Boards of Nursing Rules and Regulations for Nurse Preceptors.

BACKGROUND: The clinical education of undergraduate nursing students relies heavily on the use of staff nurses who assume the preceptor role. The best and most efficient utilization of preceptors is unknown. METHOD: This study reviewed Board of Nursing rules and regulations for all 50 states, the District of Columbia, and the U.S. territories for their published requirements regarding preceptors. Specifically, this review focused on preceptor-student and faculty-student ratios, role responsibilities, and requirements of preceptors and faculty in undergraduate precepted clinical experiences. RESULTS: Although some commonalities were noted, such as eligibility (RN licensure), degree requirements (baccalaureate), and years of experience (1 to 3), 11 states had no documented regulations. The existing documents appear to lack depth, specificity, and consistency. CONCLUSION: Because preceptors are utilized to such a great extent, the eligibility, selection, preparation, and expectations of preceptors and faculty who work with them should be more explicit. [J Nurs Educ. 2018;57(3):134-141.].

Diabetes in pregnancy and infant adiposity: systematic review and meta-analysis.

OBJECTIVE: Maternal glycaemia and anthropometry-derived newborn adiposity are strongly correlated. The children of mothers with diabetes are at greater risk of adverse metabolic health, and increased adiposity is a plausible mediator. We undertook a systematic review and meta-analysis to compare adiposity in infants of diabetic mothers (IDM) and infants of mothers without diabetes (NIDM). DESIGN: We identified observational studies reporting adiposity in IDM and NIDM. We searched references, traced forward citations and contacted authors for additional data. We considered all body composition techniques and compared fat mass, fat-free mass, body fat % and skinfold thickness. We used random effects meta-analyses and performed subgroup analyses by maternal diabetes type (type 1, type 2 and gestational) and infant sex. We examined the influence of pre-pregnancy body mass index (BMI) and conducted sensitivity analyses. RESULTS: We included data from 35 papers and over 24 000 infants. IDM have greater fat mass than NIDM (mean difference (95% CI)): 83 g (49 to 117). Fat mass is greater in infants of mothers with gestational diabetes: 62 g (29 to 94) and type 1 diabetes: 268 g (139 to 397). Insufficient studies reported data for type 2 diabetes separately. Compared with NIDM, fat mass was greater in IDM boys: 87 g (30 to 145), but not significantly different in IDM girls: 42 g (-33 to 116). There was no attenuation after adjustment for maternal BMI. CONCLUSIONS: IDM have significantly greater adiposity in comparison with NIDM. These findings are justification for studies to determine whether measures to reduce infant adiposity will improve later health.

Early preterm nutrition and the urinary metabolome in young adult life: follow-up of a randomised controlled trial.

OBJECTIVE: We aimed to test the hypothesis that early diet programmes the metabolic profile of young adults born preterm. DESIGN: We analysed banked urine samples obtained at a 20-year follow-up visit from adults that had participated as neonates in controlled trials involving randomisation within 48 hours of birth to feeds of preterm formula (PTF), banked breast milk (BBM) or term formula (TF) for 1 month postnatally. MAIN OUTCOME MEASURES: We performed proton nuclear magnetic resonance spectroscopy, analysing spectra by dietary group and sex. Orthogonal projections to latent structure discriminant analyses was used to model class differences and identify metabolites contributing to the differences between groups. Additionally, spectra were correlated with birth weight, gestational age and weight z score at 2 weeks of age. RESULTS: Of the original number of 926 trial participants, urine samples were available from 197 (21%) healthy young adults (42% men) born preterm (mean 30.7±2.8 weeks) and randomised to BBM (n=55; 28 men), TF (n=48; 14 men) and PTF (n=93; 40 men). We found no significant differences in urinary spectra between dietary groups including when stratified by sex. Correlation analysis revealed a weak association between metabolic profile and gestational age that was lost on controlling for ethanol excretion. CONCLUSIONS: We found no evidence that dietary exposures in the neonatal period influence the metabolic phenotype in young adult life.

The Search for Biomarkers of Long-Term Outcome after Preterm Birth.

Preterm birth and survival rates are rising globally, and consequently there is a growing necessity to safeguard life-long health. Epidemiological and other studies from around the world point to a higher risk of adverse adult health outcomes following preterm birth. These reports encompass morbidities in multiple domains, poorer reproductive health, and reduced longevity. The contributions of genetic inheritance, intrauterine exposures, and postnatal care practices to this altered adult phenotype are not known. Early detection is essential to implement preventive measures and to test protective antenatal and neonatal interventions to attenuate aberrant health trajectories. A satisfactory biomarker of outcome must be predictive of later functional health and ideally remain stable over the period from infancy to childhood and adult life. To date, blood pressure is the index that best fulfils these criteria. High throughput 'omic' technologies may identify biomarkers of later outcome and health risk. However, their potential can only be realized with initial investment in large, longitudinal cohort studies, which couple serial metabolomic profiling with functional health assessments across the life course.

Role of human milk oligosaccharides in Group B Streptococcus colonisation.

Group B Streptococcus (GBS) infection is a major cause of morbidity and mortality in infants. The major risk factor for GBS disease is maternal and subsequent infant colonisation. It is unknown whether human milk oligosaccharides (HMOs) protect against GBS colonisation. HMO production is genetically determined and linked to the Lewis antigen system. We aimed to investigate the association between HMOs and infant GBS colonisation between birth and postnatal day 90. Rectovaginal swabs were collected at delivery, as well as colostrum/breast milk, infant nasopharyngeal and rectal swabs at birth, 6 days and days 60-89 postpartum from 183 Gambian mother/infant pairs. GBS colonisation and serotypes were determined using culture and PCR. (1)H nuclear magnetic resonance spectroscopy was used to characterise the mother's Lewis status and HMO profile in breast milk. Mothers who were Lewis-positive were significantly less likely to be colonised by GBS (X (2)=12.50, P<0.001). Infants of Lewis-positive mothers were less likely GBS colonised at birth (X (2)=4.88 P=0.03) and more likely to clear colonisation between birth and days 60-89 than infants born to Lewis-negative women (P=0.05). There was no association between Secretor status and GBS colonisation. In vitro work revealed that lacto-N-difucohexaose I (LNDFHI) correlated with a reduction in the growth of GBS. Our results suggest that HMO such as LNDFHI may be a useful adjunct in reducing maternal and infant colonisation and hence invasive GBS disease. Secretor status offers utility as a stratification variable in GBS clinical trials.

Impact of maternal BMI and sampling strategy on the concentration of leptin, insulin, ghrelin and resistin in breast milk across a single feed: a longitudinal cohort study.

OBJECTIVES: We tested the hypothesis that there is a positive association between maternal body mass index (BMI) and the concentration of appetite-regulating hormones leptin, insulin, ghrelin and resistin in breast milk. We also aimed to describe the change in breast milk hormone concentration within each feed, and over time. SETTING: Mothers were recruited from the postpartum ward at a university hospital in London. Breast milk samples were collected at the participants' homes. PARTICIPANTS: We recruited 120 healthy, primiparous, breastfeeding mothers, aged over 18 years. Mothers who smoked, had multiple births or had diabetes were excluded. Foremilk and hindmilk samples were collected from 105 women at 1 week postpartum and 92 women at 3 months postpartum. PRIMARY AND SECONDARY OUTCOME MEASURES: We recorded maternal and infant anthropometric measurements at each sample collection and measured hormone concentrations using a multiplex assay. RESULTS: The concentration of leptin in foremilk correlated with maternal BMI at the time of sample collection, at 7 days (r=0.31, p=0.02) and 3 months postpartum (r=0.30, p=<0.00). Foremilk insulin correlated with maternal BMI at 3 months postpartum (r=0.22, p=0.04). Breast milk ghrelin and resistin were not correlated with maternal BMI. Ghrelin concentrations at 3 months postpartum were increased in foremilk compared with hindmilk (p=0.01). Concentrations of ghrelin were increased in hindmilk collected at 1  week postpartum compared with samples collected at 3 months postpartum (p=0.03). A trend towards decreased insulin concentrations in hindmilk was noted. Concentrations of leptin and resistin were not seen to alter over a feed. CONCLUSIONS: A positive correlation between maternal BMI and foremilk leptin concentration at both time points studied, and foremilk insulin at 3 months postpartum was observed. This may have implications for infant appetite regulation and obesity risk.

Development of Early Adiposity in Infants of Mothers With Gestational Diabetes Mellitus.

OBJECTIVE: Infants born to mothers with gestational diabetes mellitus (GDM) are at greater risk of later adverse metabolic health. We examined plausible candidate mediators, adipose tissue (AT) quantity and distribution and intrahepatocellular lipid (IHCL) content, comparing infants of mothers with GDM and without GDM (control group) over the first 3 postnatal months. RESEARCH DESIGN AND METHODS: We conducted a prospective longitudinal study using MRI and spectroscopy to quantify whole-body and regional AT volumes, and IHCL content, within 2 weeks and 8-12 weeks after birth. We adjusted for infant size and sex and maternal prepregnancy BMI. Values are reported as the mean difference (95% CI). RESULTS: We recruited 86 infants (GDM group 42 infants; control group 44 infants). Mothers with GDM had good pregnancy glycemic control. Infants were predominantly breast-fed up to the time of the second assessment (GDM group 71%; control group 74%). Total AT volumes were similar in the GDM group compared with the control group at a median age of 11 days (-28 cm(3) [95% CI -121, 65], P = 0.55), but were greater in the GDM group at a median age of 10 weeks (247 cm(3) [56, 439], P = 0.01). After adjustment for size, the GDM group had significantly greater total AT volume at 10 weeks than control group infants (16.0% [6.0, 27.1], P = 0.002). AT distribution and IHCL content were not significantly different at either time point. CONCLUSIONS: Adiposity in GDM infants is amplified in early infancy, despite good maternal glycemic control and predominant breast-feeding, suggesting a potential causal pathway to later adverse metabolic health. Reduction in postnatal adiposity may be a therapeutic target to reduce later health risks.

Mode of delivery and offspring body mass index, overweight and obesity in adult life: a systematic review and meta-analysis.

BACKGROUND: It has been suggested that mode of delivery, a potentially powerful influence upon long-term health, may affect later life body mass index (BMI). We conducted a systematic review and meta-analysis of the effect of Caesarean section (CS) and vaginal delivery (VD) on offspring BMI, overweight (BMI>25) and obesity (BMI>30) in adulthood. Secondary outcomes were subgroup analyses by gender and type of CS (in-labour/emergency, pre-labour/elective). METHODS: Using a predefined search strategy, Pubmed, Google Scholar and Web of Science were searched for any article published before 31(st) March 2012, along with references of any studies deemed relevant. Studies were selected if they reported birth characteristics and long-term offspring follow-up into adulthood. Aggregate data from relevant studies were extracted onto a pre-piloted data table. A random-effects meta-analysis was carried out in RevMan5. Results are illustrated using forest plots and funnel plots, and presented as mean differences or odds ratios (OR) and 95% confidence intervals. RESULTS: Thirty-five studies were identified through the search, and 15 studies with a combined population of 163,796 [corrected] were suitable for inclusion in the meta-analysis. Comparing all CS to VD in pooled-gender unadjusted analyses, mean BMI difference was 0·44 kg·m(-2) (0·17, 0·72; p = 0·002), OR for incidence of overweight was 1·26 (1·16, 1·38; p<0·00001) and OR for incidence of obesity was 1·22 (1·05, 1·42; p = 0·01). Heterogeneity was low in all primary analyses. Similar results were found in gender-specific subgroup analyses. Subgroup analyses comparing type of CS to VD showed no significant impact on any outcome. CONCLUSIONS: There is a strong association between CS and increased offspring BMI, overweight and obesity in adulthood. Given the rising CS rate worldwide there is a need to determine whether this is causal, or reflective of confounding influences. SYSTEMATIC REVIEW REGISTRATION: An a priori protocol was registered on PROSPERO (registration number: CRD42011001851).

Effect of maternal body mass index on hormones in breast milk: a systematic review.

BACKGROUND: Maternal Body Mass Index (BMI) is positively associated with infant obesity risk. Breast milk contains a number of hormones that may influence infant metabolism during the neonatal period; these may have additional downstream effects on infant appetite regulatory pathways, thereby influencing propensity towards obesity in later life. OBJECTIVE: To conduct a systematic review of studies examining the association between maternal BMI and the concentration of appetite-regulating hormones in breast milk. METHOD: Pubmed was searched for studies reporting the association between maternal BMI and leptin, adiponectin, insulin, ghrelin, resistin, obestatin, Peptide YY and Glucagon-Like Peptide 1 in breast milk. RESULTS: Twenty six studies were identified and included in the systematic review. There was a high degree of variability between studies with regard to collection, preparation and analysis of breast milk samples. Eleven of fifteen studies reporting breast milk leptin found a positive association between maternal BMI and milk leptin concentration. Two of nine studies investigating adiponectin found an association between maternal BMI and breast milk adiponectin concentration; however significance was lost in one study following adjustment for time post-partum. No association was seen between maternal BMI and milk adiponectin in the other seven studies identified. Evidence for an association between other appetite regulating hormones and maternal BMI was either inconclusive, or lacking. CONCLUSIONS: A positive association between maternal BMI and breast milk leptin concentration is consistently found in most studies, despite variable methodology. Evidence for such an association with breast milk adiponectin concentration, however, is lacking with additional research needed for other hormones including insulin, ghrelin, resistin, obestatin, peptide YY and glucagon-like peptide-1. As most current studies have been conducted with small sample sizes, future studies should ensure adequate sample sizes and standardized methodology.

Preterm birth and the metabolic syndrome in adult life: a systematic review and meta-analysis.

BACKGROUND: Preterm birth is associated with features of the metabolic syndrome in later life. We performed a systematic review and meta-analysis of studies reporting markers of the metabolic syndrome in adults born preterm. METHODS: Reports of metabolic syndrome-associated features in adults (≥18 years of age) born at <37-week gestational age and at term (37- to 42-week gestational age) were included. Outcomes assessed were BMI, waist-hip ratio, percentage fat mass, systolic (SBP) and diastolic (DBP) blood pressure, 24-hour ambulatory SBP and DBP, flow-mediated dilatation, intima-media thickness, and fasting glucose, insulin, and lipid profiles. RESULTS: Twenty-seven studies, comprising a combined total of 17,030 preterm and 295,261 term-born adults, were included. In adults, preterm birth was associated with significantly higher SBP (mean difference, 4.2 mm Hg; 95% confidence interval [CI], 2.8 to 5.7; P < .001), DBP (mean difference, 2.6 mm Hg; 95% CI, 1.2 to 4.0; P < .001), 24-hour ambulatory SBP (mean difference, 3.1 mm Hg; 95% CI, 0.3 to 6.0; P = .03), and low-density lipoprotein (mean difference, 0.14 mmol/L; 95% CI, 0.05 to 0.21; P = .01). The preterm-term differences for women was greater than the preterm-term difference in men by 2.9 mm Hg for SBP (95% CI [1.1 to 4.6], P = .004) and 1.6 mm Hg for DBP (95% CI [0.3 to 2.9], P = .02). CONCLUSIONS: For the majority of outcome measures associated with the metabolic syndrome, we found no difference between preterm and term-born adults. Increased plasma low-density lipoprotein in young adults born preterm may represent a greater risk for atherosclerosis and cardiovascular disease in later life. Preterm birth is associated with higher blood pressure in adult life, with women appearing to be at greater risk than men.

The health implications of birth by Caesarean section.

Since the first mention of fetal programming of adult health and disease, a plethora of programming events in early life has been suggested. These have included intrauterine and postnatal events, but limited attention has been given to the potential contribution of the birth process to normal physiology and long-term health. Over the last 30 years a growing number of studies have demonstrated that babies born at term by vaginal delivery (VD) have significantly different physiology at birth to those born by Caesarean section (CS), particularly when there has been no exposure to labour, i.e. pre-labour CS (PLCS). This literature is reviewed here and the processes involved in VD that might programme post-natal development are discussed. Some of the effects of CS are short term, but longer term problems are also apparent. We suggest that VD initiates important physiological trajectories and the absence of this stimulus in CS has implications for adult health. There are a number of factors that might plausibly contribute to this programming, one of which is the hormonal surge or "stress response" of VD. Given the increasing incidence of elective PLCS, an understanding of the effects of VD on normal development is crucial.

Breastfeeding after cesarean delivery: a systematic review and meta-analysis of world literature.

BACKGROUND: The rate of exclusive breastfeeding remains low in many countries. Furthermore, cesarean delivery (CD) is increasing and may affect breastfeeding success. OBJECTIVE: The objective was to conduct a systematic review and meta-analysis of observational studies to determine whether CD (prelabor or in-labor) is associated with a lower rate of breastfeeding compared with vaginal delivery (VD). DESIGN: Studies published before January 2011 that reported breastfeeding up to 6 mo postpartum and compared outcomes after CD or VD, including foreign language publications, were identified through PubMed and bibliographic review. Prespecified data were extracted independently by multiple observers. The types of CD [prelabor (elective/scheduled) or in-labor (emergency)] were compared by subgroup analyses. Potential sources of study-level bias were analyzed by using meta-regression and sensitivity analyses. RESULTS: The systematic review included 53 studies (554,568 subjects, 33 countries); 25 authors contributed additional data (245,455 subjects), and 48 studies (553,306 subjects, 31 countries) were included in the meta-analysis. Rates of early breastfeeding (any initiation or at hospital discharge) were lower after CD compared with after VD (pooled OR: 0.57; 95% CI: 0.50, 0.64; P < 0.00001) and lower after prelabor but not after in-labor CD (prelabor OR: 0.83; 95% CI: 0.80, 0.86; P < 0.00001; in-labor OR: 1.00; 95% CI: 0.97, 1.04; P = 0.86). In mothers who initiated breastfeeding, CD had no significant effect on any breastfeeding at 6 mo (OR: 0.95; 95% CI: 0.89, 1.01; P = 0.08). CONCLUSIONS: There was a negative association between prelabor CD and early breastfeeding. If breastfeeding is initiated, mode of delivery has no apparent effect on the number of mothers still breastfeeding at 6 mo. Women and health care workers should be aware of the negative associations between CD and early breastfeeding and consequent implications for infants' well-being.

Effect of breastfeeding compared with formula feeding on infant body composition: a systematic review and meta-analysis.

BACKGROUND: Early-life nutrition may influence later body composition. The effect of breastfeeding and formula feeding on infant body composition is uncertain. OBJECTIVE: We conducted a systematic review and meta-analysis of studies that examined body composition in healthy, term infants in relation to breastfeeding or formula feeding. DESIGN: PubMed was searched for human studies that reported the outcomes fat-free mass, fat mass, or the percentage of fat mass in breastfed and formula-fed infants. Bibliographies were hand searched, and authors were contacted for additional data. The quality of studies was assessed. Differences in outcomes between feeding groups were compared at prespecified ages by using fixed-effects analyses except when heterogeneity indicated the use of random-effects analyses. RESULTS: We identified 15 studies for inclusion in the systematic review and 11 studies for inclusion in the meta-analysis. In formula-fed infants, fat-free mass was higher at 3-4 mo [mean difference (95% CI): 0.13 kg (0.03, 0.23 kg)], 8-9 mo [0.29 kg (0.09, 0.49 kg)], and 12 mo [0.30 kg (0.13, 0.48 kg)], and fat mass was lower at 3-4 mo [-0.09 kg (-0.18, -0.01 kg)] and 6 mo [-0.18 kg (-0.34, -0.01 kg)] than in breastfed infants. Conversely, at 12 mo, fat mass was higher in formula-fed infants [0.29 kg (-0.03, 0.61 kg)] than in breastfed infants. CONCLUSION: Compared with breastfeeding, formula feeding is associated with altered body composition in infancy.