Matthew J. Hyde

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.

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.

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.

Maternal obesity and infant outcomes

Obesity (Body mass index (BMI) above 30) is one of the major health issues of the 21st century. Over 1.1 billion of the worlds population are now classified as obese. In the UK, women are more likely to be obese than men; over 50% of women of reproductive age are overweight or obese. Maternal obesity and the plethora of associated conditions, have a serious impact on the health and development of their offspring. In this review we describe the direct and indirect impact of maternal obesity on the health of the baby. Maternal obesity affects conception, duration and outcome of pregnancy. Offspring are at increased risk of both immediate and long term implications for health. We also briefly review potential mechanisms drawing on data from human and animal studies, and on the outcomes of clinical interventional studies.

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 1H 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.

The diabetic pregnancy and offspring BMI in childhood: a systematic review and meta-analysis.

Aims/hypothesisOffspring of mothers with diabetes are at increased risk of metabolic disorders in later life. Increased offspring BMI is a plausible mediator. We performed a systematic review and meta-analysis of studies examining offspring BMI z score in childhood in relation to maternal diabetes.MethodsPapers reporting BMI z scores for offspring of diabetic (all types, and pre- and during-pregnancy onset) and non-diabetic mothers were included. Citations were identified in PubMed; bibliographies of relevant articles were hand-searched and authors contacted for additional data where necessary. We compared offspring BMI z score with and without adjustment for maternal pre-pregnancy BMI. We performed fixed effect meta-analysis except where significant heterogeneity called for use of a random effects analysis.ResultsData were available from nine studies. In the diabetic group unadjusted mean offspring BMI z score was 0.28 higher (all diabetic mothers vs controls (95% CI 0.09, 0.47; p = 0.004; nine studies; offspring of diabetic mothers n = 927, controls n = 26,384) and with adjustment for maternal pre-pregnancy BMI, 0.07 higher (95% CI −0.15, 0.28; p = 0.54; three studies; offspring of diabetic mothers n = 244, controls n = 11,206). There was no evidence of a difference in offspring BMI z score in relation to type of diabetes (gestational vs type 1, p = 0.95).Conclusions/interpretationMaternal diabetes is associated with increased offspring BMI z score, although this is no longer apparent after adjustment for maternal pre-pregnancy BMI in the limited number of studies in which this is reported. Causal mediators of the effect of maternal diabetes on offspring outcomes remain to be established; we recommend that future research includes adjustment for maternal pre-pregnancy BMI.

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, 1H 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.

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 31st 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 163,753 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.

The long-term effects of birth by caesarean section: The case for a randomised controlled trial

Birth by caesarean section is rising rapidly around the world and is associated with a range of adverse short and long-term outcomes in offspring. The latter include features of the metabolic syndrome, type-1 diabetes, and asthma. Though there are several plausible candidate biological mechanisms, evidence of a causal relationship between mode of delivery and long-term outcomes remains lacking. Here we review the evidence to date, and examine ways in which future studies might advance understanding. We conclude that a randomised controlled trial of mode of delivery for the healthy term, cephalic pregnancy, is neither unethical nor unfeasible and should be seriously considered as the optimum means of addressing a question of great relevance to public health.