Kenny McCormick

Cardiovascular Risk Factors in Children and Young Adults Born to Preeclamptic Pregnancies: A Systematic Review

BACKGROUND AND OBJECTIVE: Preeclampsia is an independent cardiovascular risk factor for the mother, and recent studies reveal that offspring of affected pregnancies also may have an increased cardiovascular risk. Our objective was to examine evidence for increased cardiovascular risk factors in children exposed to preeclampsia in utero. METHODS: We performed a systematic review and meta-analysis on studies reporting traditional cardiovascular risk factors in those exposed to preeclampsia compared to controls. Information was extracted on the classic cardiovascular risk factors, including blood pressure, lipid profile, glucose metabolism, and BMI from articles published between 1948 and August 2011 in Medline and Embase. RESULTS: Eighteen studies provided cumulated data on 45 249 individuals. In utero exposure to preeclampsia was associated with a 2.39 mm Hg (95% confidence interval: 1.74–3.05; P < .0001) higher systolic and a 1.35 mm Hg (95% confidence interval: 0.90–1.80; P < .00001) higher diastolic blood pressure during childhood and young adulthood. BMI was increased by 0.62 kg/m2 (P < .00001). Associations were similar in children and adolescents, for different genders, and with variation in birth weight. There was insufficient evidence to identify consistent variation in lipid profile or glucose metabolism. CONCLUSIONS: Young offspring of pregnancies complicated by preeclampsia already have increased blood pressure and BMI, a finding that may need to be considered in future primary prevention strategies for cardiovascular disease.

Preterm heart in adult life: cardiovascular magnetic resonance reveals distinct differences in left ventricular mass, geometry, and function.

Background— Preterm birth leads to an early switch from fetal to postnatal circulation before completion of left ventricular in utero development. In animal studies, this results in an adversely remodeled left ventricle. We determined whether preterm birth is associated with a distinct left ventricular structure and function in humans. Methods and Results— A total of 234 individuals 20 to 39 years of age underwent cardiovascular magnetic resonance. One hundred two had been followed prospectively since preterm birth (gestational age=30.3±2.5 week; birth weight=1.3±0.3 kg), and 132 were born at term to uncomplicated pregnancies. Longitudinal and short-axis cine images were used to quantify left ventricular mass, 3-dimensional geometric variation by creation of a unique computational cardiac atlas, and myocardial function. We then determined whether perinatal factors modify these left ventricular parameters. Individuals born preterm had increased left ventricular mass (66.5±10.9 versus 55.4±11.4 g/m2; P<0.001) with greater prematurity associated with greater mass (r = −0.22, P=0.03). Preterm-born individuals had short left ventricles with small internal diameters and a displaced apex. Ejection fraction was preserved (P>0.99), but both longitudinal systolic (peak strain, strain rate, and velocity, P<0.001) and diastolic (peak strain rate and velocity, P<0.001) function and rotational (apical and basal peak systolic rotation rate, P =0.05 and P =0.006; net twist angle, P=0.02) movement were significantly reduced. A diagnosis of preeclampsia during the pregnancy was associated with further reductions in longitudinal peak systolic strain in the offspring (P=0.02, n=29). Conclusions— Individuals born preterm have increased left ventricular mass in adult life. Furthermore, they exhibit a unique 3-dimensional left ventricular geometry and significant reductions in systolic and diastolic functional parameters. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01487824.Background— Preterm birth leads to an early switch from fetal to postnatal circulation before completion of left ventricular in utero development. In animal studies, this results in an adversely remodeled left ventricle. We determined whether preterm birth is associated with a distinct left ventricular structure and function in humans. Methods and Results— A total of 234 individuals 20 to 39 years of age underwent cardiovascular magnetic resonance. One hundred two had been followed prospectively since preterm birth (gestational age=30.3±2.5 week; birth weight=1.3±0.3 kg), and 132 were born at term to uncomplicated pregnancies. Longitudinal and short-axis cine images were used to quantify left ventricular mass, 3-dimensional geometric variation by creation of a unique computational cardiac atlas, and myocardial function. We then determined whether perinatal factors modify these left ventricular parameters. Individuals born preterm had increased left ventricular mass (66.5±10.9 versus 55.4±11.4 g/m2; P 0.99), but both longitudinal systolic (peak strain, strain rate, and velocity, P <0.001) and diastolic (peak strain rate and velocity, P <0.001) function and rotational (apical and basal peak systolic rotation rate, P =0.05 and P =0.006; net twist angle, P =0.02) movement were significantly reduced. A diagnosis of preeclampsia during the pregnancy was associated with further reductions in longitudinal peak systolic strain in the offspring ( P =0.02, n=29). Conclusions— Individuals born preterm have increased left ventricular mass in adult life. Furthermore, they exhibit a unique 3-dimensional left ventricular geometry and significant reductions in systolic and diastolic functional parameters. Clinical Trial Registration— URL: . Unique identifier: [NCT01487824][1]. # Clinical Perspective {#article-title-37} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01487824&atom=%2Fcirculationaha%2F127%2F2%2F197.atom

Feeding Preterm Infants after Hospital Discharge: Growth and Development at 18 Months of Age

We have shown that preterm infants fed a preterm formula grow better than those fed a standard term infant formula after hospital discharge. The purpose of this follow-up study was to determine whether improved early growth was associated with later growth and development. Preterm infants (≤1750 g birth weight, ≤34 wk gestation) were randomized to be fed either a preterm infant formula (discharge to 6 mo corrected age), or a term formula (discharge to 6 mo), or the preterm (discharge to term) and the term formula (term to 6 mo). Anthropometry was performed at 12 wk and 6, 12, and 18 mo. Mental and psychomotor development were assessed using the Bayley Scales of Infant Development II at 18 mo. Differences in growth observed at 12 wk were maintained at 18 mo. At 18 mo, boys fed the preterm formula were 1.0 kg heavier, 2 cm longer, and had a 1.0 cm greater occipitofrontal circumference than boys fed the term formula. Boys fed the preterm formula were also 600 g heavier and 2 cm longer than girls fed the preterm formula. However, no differences were noted in MDI or PDI between boys fed the preterm formula and boys fed the term formula or between the boys fed preterm formula and girls fed the preterm formula. Overall, boys had significantly lower MDI than girls (mean difference, 6.0;p < 0.01), primarily reflecting lower scores in boys fed the term formula. Thus, early diet has long-term effects on growth but not development at 18 mo of age. Sex remains an important confounding variable when assessing growth and developmental outcome in these high-risk infants.

Feeding Preterm Infants after Hospital Discharge: Effect of Diet on Body Composition

Our purpose in this study was to examine whole body composition, using dual energy x-ray absorptiometry (DEXA) during dietary intervention in preterm infants (≤1750 g birthweight, ≤34 wk gestation). At discharge, infants were randomized to be fed either a preterm infant formula (discharge–6 mo; group A) or a term formula (discharge–6 mo; group B), or the preterm formula (discharge–term) and the term formula (term–6 mo; group C). Nutrient intake was measured between each clinic visit. To measure body composition, DEXA was used at discharge, term, 12 wk, 6 mo, and 12 mo corrected age. The data were analyzed by ANOVA. At discharge, no differences were noted in patient characteristics between groups A, B, and C. Although energy intakes were similar, protein and mineral intakes differed between groups (A > C > B;p< 0.0001). During the study, weight gain and LM gain were greater in group A than B. At 12 mo, weight, LM, FM, and BMM but not % FM or BMD were greater in group A than B. However, the effects of diet were confined to boys, with no lasting effects seen in girls. In summary, therefore, DEXA was precise enough to detect differences in whole body composition during dietary intervention. Increased weight gain primarily reflected an increase in LM and is consistent with the idea that the preterm formula more closely met protein and/or protein-energy needs in rapidly growing preterm male infants.

Right Ventricular Systolic Dysfunction in Young Adults Born Preterm

Background— Young adults born preterm have distinct differences in left ventricular mass, function, and geometry. Animal studies suggest that cardiomyocyte changes are evident in both ventricles after preterm birth; therefore, we investigated whether these young adults also have differences in their right ventricular structure and function. Methods and Results— We studied 102 preterm-born young adults followed up prospectively since birth and 132 term-born control subjects born to uncomplicated pregnancies. We quantified right ventricular structure and function by cardiovascular magnetic resonance on a 1.5-T Siemens scanner using Argus and TomTec postprocessing software. Preterm birth was associated with a small right ventricle (end diastolic volume, 79.8±13.2 versus 88.5±11.8 mL/m2; P<0.001) but greater right ventricular mass (24.5±3.5 versus 20.4±3.4 g/m2; P<0.001) compared with term-born controls, with the severity of differences proportional to gestational age (r=−0.47, P<0.001). Differences in right ventricular mass and function were proportionally greater than previously reported for the left ventricle. This was most apparent for systolic function; young adults born preterm had significantly lower right ventricular ejection fraction (57±8% versus 60±5%; P=0.006). Indeed, 21% had values below the lower limit observed in the term-born adults and 6% had mild systolic dysfunction (<45%). Postnatal ventilation accounted for some of the variation in mass but not function. Conclusions— Preterm birth is associated with global myocardial structural and functional differences in adult life, including smaller right ventricular size and greater mass. The changes are greater in the right ventricle than previously observed in the left ventricle, with potentially clinically significant impairment in right ventricular systolic function.

Early or Delayed Enteral Feeding for Preterm Growth-Restricted Infants: A Randomized Trial

BACKGROUND: Growth-restricted preterm infants are at increased risk of developing necrotizing enterocolitis (NEC) and initiation of enteral feeding is frequently delayed. There is no evidence that this delay is beneficial and it might further compromise nutrition and growth. METHODS: Infants with gestation below 35 weeks, birth weight below the 10th centile, and abnormal antenatal umbilical artery Doppler waveforms were randomly allocated to commence enteral feeds “early,” on day 2 after birth, or “late,” on day 6. Gradual increase in feeds was guided by a “feeding prescription” with rate of increase the same for both groups. Primary outcomes were time to achieve full enteral feeding sustained for 72 hours and NEC. RESULTS: Four hundred four infants were randomly assigned from 54 hospitals in the United Kingdom and Ireland (202 to each group). Median gestation was 31 weeks. Full, sustained, enteral feeding was achieved at an earlier age in the early group: median age was 18 days compared with 21 days (hazard ratio: 1.36 [95% confidence interval: 1.11–1.67]). There was no evidence of a difference in the incidence of NEC: 18% in the early group and 15% in the late group (relative risk: 1.2 [95% confidence interval: 0.77–1.87]). Early feeding resulted in shorter duration of parenteral nutrition and high-dependency care, lower incidence of cholestatic jaundice, and improved SD score for weight at discharge. CONCLUSIONS: Early introduction of enteral feeds in growth-restricted preterm infants results in earlier achievement of full enteral feeding and does not appear to increase the risk of NEC.

Adiposity Is Not Altered in Preterm Infants Fed With a Nutrient-Enriched Formula After Hospital Discharge

To determine whether adiposity was altered, body size (weight, length) and composition, determined by dual energy x-ray absorptiometry, were examined in preterm infants fed with a nutrient enriched (A, n = 56), a term infant (B, n = 57) or the nutrient enriched (discharge and term) plus the term formula (term and 6 mo; C, n = 26), and a group of breast-fed preterm infants (D, n = 25) at hospital discharge, 3, 6, and 12 mo corrected age. The results were analyzed using standard statistics. One hundred sixty-four infants (birth weight = 1406 ± 248 g, GA = 31 ± 1.7 wk) were studied. All infants underwent “catch-up,” but weight and length were greater in infants in group A compared with groups B, C, or D. More rapid and complete “catch-up” was paralleled by increased total nonfat and fat mass (g) but not percentage of fat mass. Changes in fat mass (g) were primarily explained by increased fat accretion on the legs. More rapid and complete “catch-up” growth, therefore, reflected increased nonfat and peripheral fat mass. These data do not support the hypothesis of increased or central adiposity in infants fed a nutrient-enriched formula after hospital discharge.

Feeding infants below 29 weeks’ gestation with abnormal antenatal Doppler: analysis from a randomised trial

Objective To describe feeding and gastrointestinal outcomes in growth-restricted infants <29 weeks’ gestation and to determine the rate of feed advancement which they tolerate. Design Analysis of prospectively collected data from a randomised feeding trial, the Abnormal Doppler Enteral Prescription Trial (ADEPT). Setting 54 neonatal units in the UK and Ireland. Participants 404 preterm, growth-restricted infants with abnormal antenatal Doppler studies from ADEPT. 83 infants <29 weeks and 312 infants ≥29 weeks’ gestation were included in this analysis. Interventions In ADEPT, infants were randomised to start milk ‘early’ on day 2 after birth, or ‘late’ on day 6. Subsequent feed advancement followed a regimen, which should have achieved full feeds by day 16 in the early and day 20 in the late group. Main outcome measures Full feeds were achieved later in infants <29 weeks; median age 28 days {IQR 22–40} compared with 19 days {IQR 17–23} in infants ≥29 weeks (HR 0.35, 95% CI 0.3 to 0.5). The incidence of necrotising enterocolitis was also higher in this group; 32/83 (39%) compared to 32/312 (10%) in those ≥29 weeks (RR 3.7, 95% CI 2.4 to 5.7). Infants <29 weeks tolerated very little milk for the first 10 days of life and reached full feeds 9 days later than predicted from the trial regimen. Conclusions Growth-restricted infants born <29 weeks’ gestation with abnormal antenatal Doppler failed to tolerate even the careful feeding regimen of ADEPT. A slower advancement of feeds may be required for these infants. Trial registration number ISRCTN87351483.

Zinc protoporphyrin/haem ratio and plasma ferritin in preterm infants

Objective: To study the utility of the zinc protoporphyrin/haem (ZPP/H) ratio as a measure of iron status in healthy, growing, preterm infants. Method: ZPP/H was measured in 109 well, preterm infants from the time of hospital discharge until 1 year of age (637 determinations). Results: ZPP/H was initially high, but steadily declined. This was opposite to what was expected from the known changes in iron stores during the first year of life and the observed changes in plasma ferritin. Subjects with higher ZPP/H ratios tended to have lower ferritins, but changes in ZPP/H in a given subject were poorly reflected by changes in plasma ferritin. Between 6 and 9 months of age, ZPP/H correlated with other measures of iron status, but serum ferritin concentration did not. Conclusion: Use of the ZPP/H ratio as a measure of iron status during the first year of life appears to be confounded by the developmental changes in ZPP/H, but in the later half of this period it may be a better measure of iron status than serum ferritin.

Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm

BackgroundAdults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development.MethodsCardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes.ResultsAt birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001).ConclusionPreterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health.