The prognostic accuracy of short term variation of fetal heart rate in early-onset fetal growth restriction: A systematic review.

OBJECTIVE: Cardiotocography (CTG) is an important tool for fetal surveillance in severe early-onset fetal growth restriction (FGR). Assessment of the CTG is usually performed visually (vCTG). However, it is suggested that computerized analysis of the CTG (cCTG) including short term variability (STV) could more accurately detect fetal compromise. The objective of this study was to systematically review the literature on the association between cCTG and perinatal outcome and the comparison of cCTG with vCTG. STUDY DESIGN: A systematic search was performed in MEDLINE, EMBASE and Google Scholar. Studies were included that assessed prognostic accuracy of STV or compared STV to vCTG in patients with FGR. Risk of bias and concerns about applicability were assessed with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) instrument. RESULTS: Of the 885 records identified in the search, five cohort studies (387 patients) were included. We found no randomized studies comparing STV with visual CTG in patients with FGR. The risk of bias of all studies was generally judged as 'low'. One small study found an association of low STV with neonatal acidosis. One study observed no association of STV with long-term outcome. Composite analysis of all five studies showed a non-significant relative risk for acidosis after a low STV of 1.4 (95% CI 0.6-3.2, N = 387). Further meta-analysis was hampered due to heterogeneity in outcome reporting and use of different thresholds. CONCLUSION: The evidence from the included studies did not support an association of STV and short or long term outcome. However, available data are limited and heterogeneous, and influenced by management based on STV. Solid evidence from a randomized controlled trial comparing STV with vCTG including long term infant outcome is needed before STV can be used clinically for timing of delivery in patients with FGR.

Neurodevelopmental outcomes at five years after early-onset fetal growth restriction: Analyses in a Dutch subgroup participating in a European management trial.

OBJECTIVE: The objective of this study is to explore developmental outcomes at five years after early-onset fetal growth restriction (FGR). STUDY DESIGN: Retrospective data analysis of prospective follow-up of patients of three Dutch centres, who participated in a twenty centre European randomized controlled trial on timing of delivery in early-onset FGR. Developmental outcome of very preterm infants born after extreme FGR is assessed at (corrected) age of five. RESULTS: Seventy-four very preterm FGR children underwent follow-up at the age of five. Mean gestational age at birth was 30 weeks and birth weight was 910 g, 7% had a Bayley score <85 at two years. Median five years' FSIQ was 97, 16% had a FSIQ < 85, and 35% had one or more IQ scores <85. Motor score ≤ 7 on movement ABC-II (M-ABC-II-NL) was seen in 38%. Absent or reversed end-diastolic flow, gestational age at delivery, birthweight and neonatal morbidity were related to an FSIQ < 85. Any abnormal IQ scale score was related to birthweight, male sex and severity of FGR, and abnormal motor score to male sex and bronchopulmonary dysplasia (BPD). CONCLUSIONS: Overall, median cognitive outcome at five years was within normal range, but 35% of the children had any abnormal IQ score at age five, depending on the IQ measure, and motor impairment was seen in 38% of the children. GA at delivery, birthweight, EDF prior to delivery and neonatal morbidity were the most important risk factors for cognitive outcomes.

STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction): an international consortium of randomised placebo-controlled trials.

BACKGROUND: Severe, early-onset fetal growth restriction due to placental insufficiency is associated with a high risk of perinatal mortality and morbidity with long-lasting sequelae. Placental insufficiency is the result of abnormal formation and function of the placenta with inadequate remodelling of the maternal spiral arteries. There is currently no effective therapy available. Some evidence suggests sildenafil citrate may improve uteroplacental blood flow, fetal growth, and meaningful infant outcomes. The objective of the Sildenafil TheRapy In Dismal prognosis Early onset fetal growth Restriction (STRIDER) collaboration is to evaluate the effectiveness of sildenafil versus placebo in achieving healthy perinatal survival through the conduct of randomised clinical trials and systematic review including individual patient data meta-analysis. METHODS: Five national/bi-national multicentre randomised placebo-controlled trials have been launched. Women with a singleton pregnancy between 18 and 30 weeks with severe fetal growth restriction of likely placental origin, and where the likelihood of perinatal death/severe morbidity is estimated to be significant are included. Participants will receive either sildenafil 25 mg or matching placebo tablets orally three times daily from recruitment to 32 weeks gestation. DISCUSSION: The STRIDER trials were conceived and designed through international collaboration. Although the individual trials have different primary outcomes for reasons of sample size and feasibility, all trials will collect a standard set of outcomes including survival without severe neonatal morbidity at time of hospital discharge. This is a summary of all the STRIDER trial protocols and provides an example of a prospectively planned international clinical research collaboration. All five individual trials will contribute to a pre-planned systematic review of the topic including individual patient data meta-analysis. TRIAL REGISTRATIONS: New Zealand and Australia: ACTRN12612000584831 . Registered 30/05/2012. Canada: NCT02442492 . Registered 05/05/2015. Ireland: CT 900/572/1 . Registered 15/07/2015. The Netherlands: NCT02277132 . Registered 29/09/2014. United Kingdom: ISRCTN39133303 . Registered 31/07/2014.

Endurance training increased HDL cholesteryl ester metabolism in rats.

We studied the effects of endurance training on the metabolism of high-density lipoprotein (HDL, 1.063 less than density less than 1.15 kg/l) cholesteryl ester and proteins in rats fed a cholesterol-rich (1%) semipurified diet. The HDL were labeled with 131I in the apoproteins and with cholesteryl-[1-14C]oleate in the esters. The HDL were intravenously administered to endurance-trained (n = 10) and cage-sedentary (n = 10) rats. Blood samples were taken over the next 36 h while the rats were conscious and feeding. The trained rats had higher plasma HDL cholesterol (0.72 vs. 0.28 mM) and HDL apoprotein (461 vs. 267 mg/l) concentrations than the sedentary rats. The production or disposal rate of HDL cholesteryl ester was higher in the trained rats (1.36 mumol/h) than in the sedentary rats (0.72 mumol/h), whereas the production or disposal rate of HDL apoproteins was similar in the trained (0.64 mg/h) and sedentary (0.60 mg/h) rats. The residence time of the HDL cholesteryl esters (4.72 +/- 0.22 vs. 3.37 +/- 0.21 h) and HDL apoprotein (7.65 +/- 0.36 vs. 4.55 +/- 0.28 h) was longer for the trained than for the sedentary rats. These data indicate that endurance training resulted in a significant change in the metabolism of HDL cholesteryl esters and apoproteins as well as an increase in their concentrations.

Physiological factors associated with the lower maximal oxygen consumption of master runners.

We examined the hemodynamic factors associated with the lower maximal O2 consumption (VO2max) in older formerly elite distance runners. Heart rate and VO2 were measured during submaximal and maximal treadmill exercise in 11 master [66 +/- 8 (SD) yr] and 11 young (32 +/- 5 yr) male runners. Cardiac output was determined using acetylene rebreathing at 30, 50, 70, and 85% VO2max. Maximal cardiac output was estimated using submaximal stroke volume and maximal heart rate. VO2max was 36% lower in master runners (45.0 +/- 6.9 vs. 70.4 +/- 8.0 ml.kg-1.min-1, P less than or equal to 0.05), because of both a lower maximal cardiac output (18.2 +/- 3.5 vs. 25.4 +/- 1.7 l.min-1) and arteriovenous O2 difference (16.6 +/- 1.6 vs. 18.7 +/- 1.4 ml O2.100 ml blood-1, P less than or equal to 0.05). Reduced maximal heart rate (154.4 +/- 17.4 vs. 185 +/- 5.8 beats.min-1) and stroke volume (117.1 +/- 16.1 vs. 137.2 +/- 8.7 ml.beat-1) contributed to the lower cardiac output in the older athletes (P less than or equal 0.05). These data indicate that VO2max is lower in master runners because of a diminished capacity to deliver and extract O2 during exercise.

Effects of leg press training on cycling, leg press, and running peak cardiorespiratory measures.

Six males and seven females trained 3 d per wk (30 min at 80 to 85% heart rate reserve) for 20 wk on a leg press apparatus. A progressive exercise test was administered on a cycle ergometer, leg press apparatus, and treadmill before and after training. Before training, peak oxygen consumption (VO2, ml X kg-1 X min-1) during the leg press test was higher for the males (23.9 +/- 1.60, mean +/- SE) compared to the females (19.5 +/- 2.40, P less than or equal to 0.05). Peak VO2 during the cycling (males = 36.6 +/- 2.65, females = 28.5 +/- 2.35) and treadmill (males = 39.8 +/- 2.04, females = 33.2 +/- 2.64) tests was also different between the sexes, and 30 to 40% higher than during the leg press test (P less than or equal to 0.05). Peak heart rate (beats X min-1) was not different between the sexes (P greater than 0.05), yet was 11% lower during the leg press test (165 +/- 3.5) compared to the cycling (184 +/- 2.8) and treadmill (187 +/- 1.3) tests (P less than or equal to 0.05). After training, peak VO2 during the cycling and treadmill tests increased 10 to 15%, compared to 35% during the leg press test (P less than or equal to 0.05). The only change in peak heart rate was a 6% increase during the leg press test (P less than or equal to 0.05). Although peak VO2 on the leg press apparatus was lower than on the cycle ergometer and treadmill, leg press exercise elicited a sufficient stimulus for increasing peak VO2 on the three testing modes.

Functional translation of exercise responses from graded exercise testing to exercise training.

This study attempts to develop a quantitative approach to the prescription of absolute exercise intensity during level ground ambulation (min/mile) or cycle ergometry (kpm) from responses observed during GXT. A total of 345 subjects performed GXT and exercise training sessions with either the Bruce treadmill protocol and level ground ambulation (N = 154) or cycle ergometry (N = 191). Responses from 90% of each group were used to generate equations for predicting training pace (or power output) from the time (or power output) during the GXT when target HR was achieved. FAI was also included in the prediction of training pace (or power output). The remaining 10% of subjects in each group were used to cross-validate the prediction equations. The correlation between the time (or power output) during GXT when the training HR was observed and the pace of ambulation (or power output) was 0.70 for treadmill walking and 0.88 for cycle-cycle. Correlations were increased by the addition of FAI to the prediction equation. The results of this investigation suggest that the absolute intensity of exercise for training can be predicted accurately from GXT results.

Effects of exercise training on plasma lipids and lipoproteins in rats.

We studied the effects of exercise training on plasma lipid and lipoprotein concentrations of rats on a high-fat and high-cholesterol diet. Twelve weeks of training occurred at moderate [Mod-Exer, 70% peak O2 consumption (VO2)] and high (High-Exer, 82% peak VO2) intensities. The duration of daily training sessions was adjusted to maintain equivalent energy expenditure between groups. Following training, body weight and lean body mass were 10% lower in the High-Exer group than the Mod-Exer or control groups. Compared with control values, carcass fat content was 33% lower for both trained groups. The oxidative capacity of skeletal muscle was approximately 30% greater in the trained groups compared with the control group. Total cholesterol, high density lipoprotein cholesterol, and total triglyceride concentrations in plasma were not different between the trained groups, but were 33-47% lower compared with the control group. The exercise-induced changes in plasma lipid and lipoprotein concentrations may be a result of a change in preferred substrate utilization in skeletal muscle toward a greater oxidation of lipid.

Exercise prescription for the cardiac patient: an update.

Exercise prescription for patients after myocardial infarction and for those after coronary artery bypass grafting is contrasted with prescription for healthy adults. Calculation of target training heart rate and the rating of perceived exertion scale for the cardiac patient are examined. The authors discuss in detail exercise prescription for the cardiac patient during in-patient, outpatient, and community-based programs. A well-rounded approach including flexibility, strength, and aerobic components is emphasized.

Daily physical activity patterns of prepubertal children involved in a vigorous exercise program.

The purpose of the present investigation was to examine the effects of a vigorous physical activity program on daily physical activity patterns of 59 7-year-old children divided into experimental (n = 26) and control (n = 33) groups. The experimental group participated in a 25-min vigorous, aerobic exercise session 4 days per week, while the control group maintained their normal daily activities, which included a 1 day per week physical education class, for 8 months. The intensity of each experimental exercise session and each control physical education class was determined by fitting Exersentry heart rate devices to two different children randomly selected from each group without replacement. Daily activity patterns were determined using minute-by-minute heart rates calculated from a 12-h EKG recorded from 8 a.m. to 8 p.m. using an Oxford Instruments ambulatory monitor. Analysis of the Exersentry data demonstrated significantly higher heart rates (P less than 0.05) during the experimental exercise session compared to the control physical education class, except during pre-exercise. Analysis of the 12-h EKG data (n = 720 min) revealed the experimental group spent significantly more time (P less than 0.05) at heart rates greater than 160 bts X min-1 (35 +/- 6 min, experimental; 21 +/- 3 min, control) during the intervention program. No significant group differences (P greater than 0.05) were observed in 12-h heart rate data collected prior to initiation of the intervention program. These data suggest that a vigorous physical activity program resulted in differences in the daily physical activity patterns of 7-year-old children.

Heart rate response to bicycle ergometer exercise in children ages 6-7 years.

The purpose of the present investigation was to compare the heart rate response of pre-pubertal males and females during rest, steady-rate power output, peak power output, and recovery. Sixty-six children (38 males and 28 females) ages 6-7 years performed a continuous bicycle ergometer exercise test, including 4 min of steady-rate work (males = 15.3 +/- 0.17 W.min-1, females = 15.0 +/- 0.16 W.min-1) followed by a progressive increase in resistance until volitional fatigue, and a 5-min recovery period immediately following termination of exercise. Mean steady-rate heart rate response of 119.0 +/- 1.75 beats.min-1 for males was significantly (P less than 0.05) lower than the females (132.1 +/- 2.92 beats.min-1). Peak heart rate response was similar between the sexes (190.1 +/- 1.21 and 192.1 +/- 1.73 beats.min-1 for males and females, respectively; P greater than 0.05). Sex differences in heart rate recovery from peak values were significant (P less than 0.05) during the first 3 min of the 5-min recovery period, but not thereafter (P greater than 0.05). It was concluded that sex differences in heart rate response were present in these prepubertal children at rest, during steady-rate power output, and during the first 3 min of recovery.