Maggie M. Sopper

Nutrition and exercise prevent excess weight gain in overweight pregnant women.

PURPOSE To determine the effect of a Nutrition and Exercise Lifestyle Intervention Program (NELIP) for overweight (OW) and obese (OB) pregnant women on pregnancy weight gain, birth weight, and maternal weight retention at 2 months postpartum. METHODS This is a single-arm intervention matched by prepregnant body mass index, age, and parity to a historical cohort (4:1). Women with a prepregnancy body mass index of > or = 25.0 kg x m(-2) (N = 65) participated in a NELIP starting at 16-20 wk of pregnancy, continuing until delivery. NELIP consisted of an individualized nutrition plan with total energy intake of approximately 2000 kcal x d(-1) (8360 kJ x d(-1)) and 40%-55% of total energy intake from carbohydrate. Exercise consisted of a walking program (30% HR reserve), three to four times per week, using a pedometer to count steps. Matched historical cohort (MC; N = 260) was from a large local perinatal database. RESULTS Weight gained by women on the NELIP was 6.8 +/- 4.1 kg (0.38 +/- 0.2 kg x wk(-1)), with a total pregnancy weight gain of 12.0 +/- 5.7 kg. Excessive weight gain occurred before NELIP began at 16 wk of gestation. Eighty percent of the women did not exceed recommended pregnancy weight gain on NELIP. Weight retention at 2 months postpartum was 2.2 +/- 5.6 kg with no difference between the OW and the OB women on NELIP. Mean birth weight was not different between NELIP (3.59 +/- 0.5 kg) and MC (3.56 +/- 0.6 kg, P > 0.05). CONCLUSIONS NELIP reduces the risk of excessive pregnancy weight gain with minimal weight retention at 2 months postpartum in OW and OB women. This intervention may assist OW and OB women in successful weight control after childbirth.

Phosphorylation state of the native high-molecular-weight neurofilament subunit protein from cervical spinal cord in sporadic amyotrophic lateral sclerosis

The intraneuronal aggregation of phosphorylated high‐molecular‐weight neurofilament protein (NFH) in spinal cord motor neurons is considered to be a key pathological marker of amyotrophic lateral sclerosis (ALS). In order to determine whether this observation is due to the aberrant or hyper‐phosphorylation of NFH, we have purified and characterized NFH from the cervical spinal cords of ALS patients and controls. We observed no differences between ALS and normal controls in the physicochemical properties of NFH in Triton X‐100 insoluble protein fractions, with respect to migration patterns on 2D‐iso electrofocusing (IEF) gels, the rate of Escherichia coli alkaline phosphatase mediated dephosphorylation, or the rate of calpain‐mediated proteolysis. The rate of calpain‐mediated proteolysis was unaffected by either exhaustive NFH dephosphorylation or by the addition of calmodulin to the reaction. Phosphopeptides and the phosphorylated motifs characterized by liquid chromatography tandem mass spectroscopy (LC/MS/MS) analysis demonstrated that all the phosphorylated residues found in ALS NFH were also found to be phosphorylated in normal human NFH samples. Hence, we have observed no difference in the physicochemical properties of normal and ALS NFH extracted from cervical spinal cords, suggesting that the perikaryal aggregation of highly phosphorylated NF in ALS neurons reflects the aberrant somatotopic localization of normally phosphorylated NFH.

Microtubule-associated tau protein positive neuronal and glial inclusions in ALS

Background: The authors compared tau protein deposition in the frontal cortex of patients with cognitive impairment of amyotrophic lateral sclerosis (ALSci) (n = 6), cognitively intact patients with ALS (n = 6), and age-matched controls (n = 6) in order to determine the pathologic substrate of ALSci. Methods: Archival paraffin-embedded tissue was examined using Gallyas staining and immunostaining for tau-1 (phosphorylation-dependent tau epitope), tau-2 (phosphorylation independent), Alzheimer-specific tau phosphoepitopes (AT 8; ser396 phosphorylation), β-amyloid, glial fibrillary acid protein, SMI 31 (recognizing phosphorylated NFH), α-synuclein, or ubiquitin. Results: Tau immunoreactive astrocytic and dense neuronal inclusions were found in both ALS and ALSci, although to a greater extent in ALSci. Superficial linear spongiosis and Gallyas-positive intraneuronal aggregates, immunoreactive with tau-1 and AT 8 but rarely to ser396 tau, were unique to ALSci. Dense extracellular aggregates were observed by both Gallyas staining and tau-1 immunostaining. Tufted degenerating astrocytes containing tau-1 and AT 8 immunoreactive aggregates and, rarely, dense Gallyas positive neuritic plaques immunoreactive with tau-1 and AT 8, but not with ser396 tau or β-amyloid, were observed in ALSci. Tau positive glial coiled bodies were observed in the deep cortical layers and adjacent subcortical white matter in ALSci. Although 3R and 4R tau mRNA isoforms were expressed to similar levels in the frontal cortex of all cases, the total amount of tau mRNA was increased in both ALS and ALSci. Both gray and white matter soluble tau protein expression was similar among control, ALS, and ALSci cases. Conclusions: Cognitive dysfunction in ALS may reflect abnormal tau protein metabolism.

Development and validation of exercise target heart rate zones for overweight and obese pregnant women

Validated target heart rate (THR) zones for exercise prescription for overweight and obese pregnant women have not been developed. The purposes of this study were to determine if heart rate reserve (HRreserve) is best described by aerobic capacity at peak exercise or by aerobic capacity reserve (VO2 reserve) and to develop and validate THR zones for light-intensity exercise (20%-39%VO2 reserve) in sedentary overweight and obese pregnant women. One hundred six women between 16 and 20 weeks gestation with medical clearance performed a progressive treadmill test to volitional fatigue (peak). Data from every 4th subject were used for cross-validation. Two linear regression equations were performed for each subject, then pooled to obtain mean group values (+/- SD): %HRreserve vs. %VO2 peak and %HRreserve vs. %VO2 reserve. THR zones equivalent to 20%-39%VO2 reserve were developed and validated based on the strongest relationship. %HRreserve had a stronger linear relationship with %VO2 reserve (y = 1.046x -7.561; R2 = 0.741) than %VO2 peak (y = 1.259x -28.795; R2 = 0.604). Validated THR ranges for sedentary overweight and obese pregnant women are 102-124 beats.min-1 (20-29 years of age) and 101-120 beats.min-1 (30-39 years of age), representing an exercise intensity of 20%-39%VO2 reserve as recommended by the American College of Sports Medicine for previously sedentary pregnant women. Overweight and obese women who are medically prescreened can exercise during pregnancy within our validated THR zones. The relationship between HR and VO2 remains strong, but the two are not equivalent in this population group.

Timing of excessive pregnancy-related weight gain and offspring adiposity at birth.

OBJECTIVE: To evaluate whether the timing of excessive maternal weight gain in a cohort of women following current guidelines for healthy living during pregnancy affects neonatal adiposity at birth. METHODS: One hundred seventy-two healthy women who were at least 18 years old with body mass indexes (BMIs) of at least 18.5 were recruited between 16 weeks and 20 weeks of gestation. The cohort followed healthy living guidelines during pregnancy and were retrospectively grouped according to 2009 Institute of Medicine guidelines for weight gain in the first and second halves of pregnancy: 1) appropriate gestational weight gain (ie, within Institute of Medicine recommendations) in the first and second halves of pregnancy (“overall appropriate”); 2) appropriate gestational weight gain in the first half of pregnancy and excessive gestational weight gain in the second half of pregnancy (“late excessive”); 3) excessive gestational weight gain in the first half of pregnancy and appropriate gestational weight gain in the second half of pregnancy (“early excessive”); and 4) excessive gestational weight gain throughout pregnancy (“overall excessive”). Primary measures included neonatal weight, length, BMI, and body fat at birth measured 6–18 hours after delivery. Neonatal body fat greater than 14% was considered excessive. RESULTS: Neonates of women who gained excessively in the first half of pregnancy exhibited greater heel-crown length, birth weight, and excessive body fat (“early excessive” 17.5±3.1%, “overall excessive” 18.7±3.3%) compared with those born to women who gained appropriately (“overall appropriate” 13.2±4.1%; “late excessive” 14.7±3.3%; P<.01). Neonates of women who gained excessively in the first half of pregnancy had an increased risk (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.35–5.17) of elevated body fat at birth compared with neonates of women with total excessive weight gain (OR 1.49, 95% CI 0.80–2.79). CONCLUSION: Timing of excessive weight gain is an important factor influencing neonatal morphometrics. Prevention of early excessive weight gain should be encouraged in the period before conception and reinforced early in pregnancy. LEVEL OF EVIDENCE: II

Effect of exercise intensity and duration on capillary glucose responses in pregnant women at low and high risk for gestational diabetes

Exercise may influence glucose metabolism during pregnancy. We examined the effect of exercise intensity and duration on capillary glucose responses in pregnant women at low and high risk for gestational diabetes mellitus (GDM) who followed a modified GDM meal plan.

Nutrition and Exercise Reduce Excessive Weight Gain in Normal-Weight Pregnant Women

PURPOSE This study aimed to evaluate the effect of an exercise program of two different intensities, with nutritional control, on gestational weight gain (GWG), infant birth weight, and maternal weight retention at 2 months postpartum (2 mopp). METHODS Pregnant women (prepregnancy body mass index = 18.5-24.9 kg·m) were randomized at study entry (16-20 wk of gestation) to a low-intensity (LI, 30% HR reserve (HRR), n = 23) or moderate-intensity (MI, 70% HRR, n = 26) exercise program, with nutritional control. The exercise program consisted of walking sessions three to four times per week, gradually increasing exercise time from 25 to 40 min per session. Forty-five normal-weight women who did not participate in any structured exercise program during pregnancy and had singleton births were used as a historical control group. RESULTS Total GWG was higher in the control group (18.3 ± 5.3 kg) compared with the LI (15.3 ± 2.9 kg, P = 0.01) and MI (14.9 ± 3.8 kg, P = 0.003) groups. During the intervention, GWG was similar in both intervention groups, with weekly rates of weight gain of 0.49 ± 0.1 and 0.47 ± 0.1 kg·wk in the LI and MI groups, respectively. Excessive GWG during the intervention was prevented in 70% of the women in the LI group and 77% of those in the MI group. Excessive GWG occurred before the intervention began. At 2 mopp, 18% and 28% of the women in the LI and MI groups, respectively, retained ≤2.0 kg compared with only 7% of those in the control group. Infant birth weight was not different between the groups. CONCLUSIONS Results suggest that a prenatal nutrition and exercise program regardless of exercise intensity, reduced excessive GWG and decreased weight retention at 2 mopp in women of normal weight before pregnancy.

Postpartum Exercise Regardless of Intensity Improves Chronic Disease Risk Factors

PURPOSE Women who are unable to return to a healthy weight by 6 months postpartum increase their risk factors for the development of chronic disease (CD; including metabolic syndrome, obesity, and cardiovascular disease). In a prospective randomized intervention study, we examined the effect of exercise intensity on risk factors for CD in the postpartum. We hypothesized that women receiving an intervention targeting healthy weight loss would have improved CD risk factors compared with women not receiving the intervention. Further, we hypothesized that nutrition control and moderate-intensity exercise would have the greatest improvement in CD risk factors versus low-intensity exercise. METHODS Women were randomly assigned to a nutrition plus low-intensity (30% HR reserve; n = 20) or moderate-intensity (70% HR reserve; n = 20) exercise intervention group. The program consisted of supervised walking for 45 min, three to four times per week for 16 wk. All women were screened for CD at the beginning (7-8 wk postpartum) and at the end (23-25 wk postpartum) of the study. A historical control group of 20 sedentary postpartum women was matched by body mass index, age, and parity. RESULTS The low- and moderate-intensity groups lost more body mass (-4.2 ± 4.0 and -5.0 ± 2.9 kg, respectively) compared with the control group (-0.1 ± 3.3 kg, P < 0.01). Plasma low-density lipoprotein was reduced for the low- and moderate-intensity groups (-0.29 ± 0.21 and -0.28 ± 0.17 mmol · L) compared with the control group (0.03 ± 0.18 mmol · L, P = 0.015). In addition, glucose concentrations were reduced and adiponectin concentrations increased (P = 0.037), regardless of exercise intensity, although the sedentary controls remained unchanged or at increased risk for CD. CONCLUSIONS Women receiving a postpartum intervention targeting healthy weight loss, regardless of exercise intensity, improved CD risk factors compared with women not receiving the intervention.

Walking Program of Low or Vigorous Intensity During Pregnancy Confers an Aerobic Benefit

Walking is the most popular activity during pregnancy and may confer an aerobic benefit. However, the minimum intensity threshold of a maternal walking program for an aerobic conditioning response is unknown. The purpose was to examine the effect of a walking program of a low-intensity (LI, 30% heart rate reserve, HRR) or vigorous-intensity (VI, 70%HRR) on maternal cardiorespiratory responses to a standard submaximal treadmill test. Normal weight pregnant women were randomized at study entry (16-20 weeks of gestation) to the LI (n=23) or VI (n=21) walking program, with nutritional control. Participants performed a steady-state treadmill exercise test at their prescribed intensity pre- and post-intervention (34-36 weeks) to evaluate changes in cardiorespiratory responses. Increasing body mass due to pregnancy was similar between the groups throughout the study. From pre- to post-intervention, relative (mL kg - 1 min - 1) VO2 and VCO2 during steady-state submaximal treadmill exercise did not change in the LI group but decreased in the VI group (- 1.25±2.71, p=0.02 and - 1.50±2.64, p=0.005, respectively). Both groups presented increases in oxygen pulse (p≤0.002). Our results showed that the energy cost of walking was not affected by the increase in maternal body weight in the LI group and was decreased in the VI group, suggesting an aerobic conditioning response in both groups, although the VI group presented a greater response. All women presented similar body mass throughout the intervention and delivered healthy babies, indicating that a prenatal walking program of low or vigorous intensity, combined with healthy eating habits, is safe and beneficial to the mother and fetus.

Sequestration of nNOS in neurofilamentous aggregate bearing neurons in vitro leads to enhanced NMDA-mediated calcium influx.

The significance of copper/zinc superoxide dismutase (SOD1) and neuronal nitric oxide synthase (nNOS) co-localization to neurofilamentous (NF) aggregates in amyotrophic lateral sclerosis (ALS) is unknown. In this study, we have used dissociated motor neurons from either C57BL/6 or mice that over-express the human low molecular weight neurofilament protein (hNFL+/+) to examine the relationship between NF aggregate formation, SOD1 and nNOS co-localization, and the regulation of NMDA-mediated calcium influx in vitro. The intracellular distribution of NF aggregates, SOD1 and nNOS was examined by confocal microscopy and NMDA-induced alterations in intracellular calcium levels using either Oregon green fluorescence or FURA-2 photometric imaging. Cell death was assessed using an antibody to activated caspase-3. C57 Bl/6 motor neurons expressed nNOS in a punctate manner, whereas SOD1 was distributed homogeneously throughout the cytosol. In contrast, hNFL+/+ motor neurons demonstrated co-localization of SOD1 and nNOS by day 9 post-plating, preceding the formation of NF aggregates. Both proteins co-localized to NF aggregates once formed. With NMDA stimulation, aggregate-bearing hNFL+/+ motor neurons demonstrated significant increases in intracellular calcium, whereas only a minimal alteration in intracellular calcium was observed in C57 Bl/6 neurons. Following stimulation with 100 microM NMDA, 75.5+/-5.5% of hNFL+/+ neurons became apoptotic, whereas only 16.3+/-5.3% of C57 Bl/6 were. These observations suggest that the presence of NF aggregates results in a failure of regulation of NMDA-mediated calcium influx, and that this occurs due to the sequestration of nNOS to the NF aggregate, preventing its down-regulation of the NMDA receptor.