Kathleen M. Gustafson

DHA supplementation and pregnancy outcomes

BACKGROUND Observational studies associate higher intakes of n-3 (omega-3) long-chain polyunsaturated fatty acids (LCPUFAs) during pregnancy with higher gestation duration and birth size. The results of randomized supplementation trials using various n-3 LCPUFA sources and amounts are mixed. OBJECTIVE We tested the hypothesis that 600 mg/d of the n-3 LCPUFA docosahexaenoic acid (DHA) can increase maternal and newborn DHA status, gestation duration, birth weight, and length. Safety was assessed. DESIGN This phase III, double-blind, randomized controlled trial was conducted between January 2006 and October 2011. Women (n = 350) consumed capsules (placebo, DHA) from <20 wk of gestation to birth. Blood (enrollment, birth, and cord) was analyzed for red blood cell (RBC) phospholipid DHA. The statistical analysis was intent-to-treat. RESULTS Most of the capsules were consumed (76% placebo; 78% DHA); the mean DHA intake for the treated group was 469 mg/d. In comparison with placebo, DHA supplementation resulted in higher maternal and cord RBC-phospholipid-DHA (2.6%; P < 0.001), longer gestation duration (2.9 d; P = 0.041), and greater birth weight (172 g; P = 0.004), length (0.7 cm; P = 0.022), and head circumference (0.5 cm; P = 0.012). In addition, the DHA group had fewer infants born at <34 wk of gestation (P = 0.025) and shorter hospital stays for infants born preterm (40.8 compared with 8.9 d; P = 0.026) than did the placebo group. No safety concerns were identified. CONCLUSIONS A supplement of 600 mg DHA/d in the last half of gestation resulted in overall greater gestation duration and infant size. A reduction in early preterm and very-low birth weight could be important clinical and public health outcomes of DHA supplementation. This trial was registered at clinicaltrials.gov as NCT00266825.

Long-term effects of LCPUFA supplementation on childhood cognitive outcomes

BACKGROUND The effect of long-chain polyunsaturated fatty acid (LCPUFA) intake on cognitive development is controversial. Most randomized trials have assessed cognition at 18 mo, although significant development of cognitive abilities (early executive function) emerge later. OBJECTIVE The objective was to evaluate cognition beyond 18 mo and longitudinal cognitive change from 18 mo to 6 y in children who were fed variable amounts of docosahexaenoic acid (0.32%, 0.64%, and 0.96% of total fatty acids) and arachidonic acid (ARA; 0.64%) compared with children who were not fed LCPUFA as infants. DESIGN Eighty-one children (19 placebo, 62 LCPUFA) who participated in a double-blind, randomized trial of LCPUFA supplementation as infants were re-enrolled at 18 mo and tested every 6 mo until 6 y on age-appropriate standardized and specific cognitive tests. RESULTS LCPUFA supplementation did not influence performance on standardized tests of language and performance at 18 mo; however, significant positive effects were observed from 3 to 5 y on rule-learning and inhibition tasks, the Peabody Picture Vocabulary Test at 5 y, and the Weschler Primary Preschool Scales of Intelligence at 6 y. Effects of LCPUFAs were not found on tasks of spatial memory, simple inhibition, or advanced problem solving. CONCLUSIONS The data from this relatively small trial suggest that, although the effects of LCPUFAs may not always be evident on standardized developmental tasks at 18 mo, significant effects may emerge later on more specific or fine-grained tasks. The results imply that studies of nutrition and cognitive development should be powered to continue through early childhood. This parent trial was registered at clinicaltrials.gov as NCT00266825.

Aerobic exercise during pregnancy influences fetal cardiac autonomic control of heart rate and heart rate variability

BACKGROUND Previous studies using ultrasound technology showed that fetal heart rate (HR) may be responsive to maternal aerobic exercise. Although it is recognized that cardiac autonomic control may be influenced by the intrauterine environment, little is known about how maternal exercise affects fetal heart development. AIMS This study tested the hypothesis that regular maternal exercise throughout gestation influences fetal cardiac autonomic control of HR and heart rate variability (HRV) when compared to fetuses of non-exercising women. STUDY DESIGN Magnetocardiograms (MCGs) were recorded using a dedicated fetal biomagnetometer at 28, 32 and 36 weeks gestational age (GA) from 26 regularly exercising (>30 min of aerobic exercise, 3x per week) and 35 healthy, non-exercising pregnant women. Fetal MCG was isolated and normal R-peaks were marked to derive fetal HR and HRV in the time and frequency domains. We applied a mixed-effects model to investigate the effects of exercise, GA and fetal activity state. RESULTS At 36 weeks GA, during the active fetal state, fetal HR was significantly lower in the exercise group (p=<0.0006). Post-hoc comparisons showed significantly increased HRV in the exercise group during the active fetal state at 36 weeks GA for both time and frequency domain measures. CONCLUSION These results indicate that regular maternal exercise throughout gestation results in significantly lower fetal HR and increased HRV.

Regular maternal exercise dose and fetal heart outcome.

PURPOSE Our previous research found lower fetal HR and increased HR variability (HRV) in women who exercised during pregnancy. This finding is similar to the adult heart training response at rest due to aerobic exercise. Dose-response associations have been found between physical activity and cardiorespiratory fitness in adults. Therefore, our objective was to determine whether there is a dose-response relationship between maternal physical activity and fetal HR, HRV, and sympathovagal balance. METHODS Pregnant women completed a physical activity questionnaire and magnetocardiogram (magnetic correlate to ECG) recordings at 36-wk gestational age. Women reported the duration, intensity, and frequency of each activity for each month of pregnancy as well as 3 months before pregnancy. These values were used to calculate maternal physical activity measures for each participant. Relationships between fetal HR, HRV, and sympathovagal balance at 36-wk gestational age and maternal physical activity (n = 50 pairs) during the third trimester were assessed by Spearman correlations. Regression analysis was performed to further examine these relationships after controlling for maternal and fetal covariates (maternal age, maternal resting HR, maternal weight gain, prepregnancy body mass index (BMI), and fetal activity state). RESULTS The regression analyses showed that maternal physical activity intensity (kcal·min(-1)) was negatively associated with HR in the active fetal state (P < 0.05), and physical activity duration (minutes during the third trimester) was positively associated with fetal HRV (P < 0.05). There were no statistically significant relationships with maternal physical activity on measures of fetal sympathovagal balance. CONCLUSIONS Maternal physical activity dose during the third trimester is associated with resting fetal heart effects similar to a trained response. Future studies on the health benefits of this fetal response are highly warranted.

Fetal cardiac autonomic control during breathing and non-breathing epochs: The effect of maternal exercise

We explored whether maternal exercise during pregnancy moderates the effect of fetal breathing movements on fetal cardiac autonomic control assessed by metrics of heart rate (HR) and heart rate variability (HRV). Thirty women were assigned to Exercise or Control group (n=15/group) based on the modifiable physical activity questionnaire (MPAQ). Magnetocardiograms (MCG) were recorded using a dedicated fetal biomagnetometer. Periods of fetal breathing activity and apnea were identified using the fetal diaphragmatic magnetomyogram (dMMG) as a marker. MCG R-waves were marked. Metrics of fetal HR and HRV were compared using 1 breathing and 1 apneic epoch/fetus. The main effects of group (Exercise vs. Control) and condition (Apnea vs. Breathing) and their interactions were explored. Fetal breathing resulted in significantly lower fetal HR and higher vagally-mediated HRV. Maternal exercise resulted in significantly lower fetal HR, higher total HRV and vagally-mediated HRV with no difference in frequency band ratios. Significant interactions between maternal exercise and fetal breathing were found for metrics summarizing total HRV and a parasympathetic metric. Post hoc comparison showed no group difference during fetal apnea. Fetal breathing was associated with a loss of Total HRV in the Control group and no difference in the Exercise group. Both groups show enhanced vagal function during fetal breathing; greater in the Exercise group. During in utero breathing movements, the fetus of the exercising mother has enhanced cardiac autonomic function that may give the offspring an adaptive advantage.

Aerobic exercise during pregnancy influences infant heart rate variability at one month of age

BACKGROUND Previously, we reported that regular maternal aerobic exercise during pregnancy was associated with lower fetal heart rate (HR) and higher heart rate variability (HRV) at 36weeks gestation. We now report the effect of maternal exercise on infant HR and HRV in subjects who remained active in the study at the one-month follow up visit. AIMS We aimed to determine whether differences in fetal cardiac autonomic control related to maternal physical activity were an in utero phenomenon or would persist 1month after birth. STUDY DESIGN Magnetocardiograms (MCGs) of infants born to regularly exercising (≥30min of aerobic activity, 3 times per week; N=16) and non-exercising (N=27) pregnant women were recorded using a fetal biomagnetometer. Normal R-peaks were marked to derive infant HR and HRV in time and frequency domains, including the root mean square of successive differences (RMSSD), the standard deviation of normal-to-normal interbeat intervals (SDNN), and power in the low frequency (LF) and high frequency (HF) bands. Group differences were examined with Students t-tests. RESULTS Infants born to exercising women had significantly higher RMSSD (P=0.010), LF power (P=0.002), and HF power (P=0.004) than those born to women who did not engage in regular physical activity while pregnant. CONCLUSION Infants born to women who participated in regular physical activity during pregnancy continued to have higher HRV in the infant period. This suggests that the developing cardiac autonomic nervous system is sensitive to the effects of maternal physical activity and is a target for fetal programming.

Characterization of the Fetal Diaphragmatic Magnetomyogram and the Effect of Breathing Movements on Cardiac Metrics of Rate and Variability

Breathing movements are one of the earliest fetal motor behaviors to emerge and are a hallmark of fetal well-being. Fetal respiratory sinus arrhythmia (RSA) has been documented but efforts to quantify the influence of breathing on heart rate (HR) and heart rate variability (HRV) are difficult due to the episodic nature of fetal breathing activity. We used a dedicated fetal biomagnetometer to acquire the magnetocardiogram (MCG) between 36 and 38 weeks gestational age (GA). We identified and characterized a waveform observed in the raw data and independent component decomposition that we attribute to fetal diaphragmatic movements during breathing episodes. RSA and increased high frequency power in a time-frequency analysis of the IBI time-series was observed during fetal breathing periods. Using the diaphragmatic magnetomyogram (dMMG) as a marker, we compared time and frequency domain metrics of heart rate and heart rate variability between breathing and non-breathing epochs. Fetal breathing activity resulted in significantly lower HR, increased high frequency power, greater sympathovagal balance, increased short-term HRV and greater parasympathetic input relative to non-breathing episodes confirming the specificity of fetal breathing movements on parasympathetic cardiac influence. No significant differences between breathing and non-breathing epochs were found in two metrics reflecting total HRV or very low, low and intermediate frequency bands. Using the fetal dMMG as a marker, biomagnetometry can help to elucidate the electrophysiologic mechanisms associated with diaphragmatic motor function and may be used to study the longitudinal development of human fetal cardiac autonomic control and breathing activity.

Effects of docosahexaenoic acid supplementation during pregnancy on fetal heart rate and variability: a randomized clinical trial.

DHA (22:6n-3) supplementation during infancy has been associated with lower heart rate (HR) and improved neurobehavioral outcomes. We hypothesized that maternal DHA supplementation would improve fetal cardiac autonomic control and newborn neurobehavior. Pregnant women were randomized to 600 mg/day of DHA or placebo oil capsules at 14.4 (+/-4) weeks gestation. Fetal HR and HRV were calculated from magnetocardiograms (MCGs) at 24, 32 and 36 weeks gestational age (GA). Newborn neurobehavior was assessed using the Neonatal Behavioral Assessment Scale (NBAS). Post-partum maternal and infant red blood cell (RBC) DHA was significantly higher in the supplemented group as were metrics of fetal HRV and newborn neurobehavior in the autonomic and motor clusters. Higher HRV is associated with more responsive and flexible autonomic nervous system (ANS). Coupled with findings of improved autonomic and motor behavior, these data suggest that maternal DHA supplementation during pregnancy may impart an adaptive advantage to the fetus.

Docosahexaenoic acid and cognitive function: Is the link mediated by the autonomic nervous system?

Docosahexaenoic acid is a long-chain polyunsaturated fatty acid that is found in large quantity in the brain and which has repeatedly been observed to be related in positive ways to both cognitive function and cardiovascular health. The mechanisms through which docosahexaenoic acid affects cognition are not well understood, but in this article, we propose a hypothesis that integrates the positive effects of docosahexaenoic acid in the cognitive and cardiovascular realms through the autonomic nervous system. The autonomic nervous system is known to regulate vital functions such as heart rate and respiration, and has also been linked to basic cognitive components related to arousal and attention. We review the literature from this perspective, and delineate the predictions generated by the hypothesis. In addition, we provide new data showing a link between docosahexaenoic acid and fetal heart rate that is consistent with the hypothesis.

Maternal physical activity mode and fetal heart outcome

BACKGROUND Maternal leisure-time physical activity (LTPA) improves cardiac autonomic function in the fetus. The specific physical activity attributes (e.g., mode) that produce this benefit are not well understood. AIM To determine if more time spent performing non-continuous LTPA during pregnancy is significantly associated with lower fetal heart rate (HR) and increased heart rate variability (HRV). STUDY DESIGN This paper presents a retrospective analysis of previously reported data. Fetal magnetocardiograms (MCG) were recorded from 40 pregnant women at 36-wk gestational age. OUTCOME MEASURES Metrics of fetal HR and HRV, self-reported min of continuous and non-continuous LTPA performed during the 3-months preceding the 36-wk assessment point and covariates (maternal weight change pre to 36-wk, age, and resting HR and fetal activity state during MCG recordings. RESULTS Positive correlations were significant (p<0.05) between min of continuous LTPA, the time domain metrics that describe fetal overall HRV, short-term HRV and a frequency domain metric that reflects vagal activity. Time spent in non-continuous LTPA was positively correlated (p<0.05) with two HRV metrics that reflect fetal overall HRV. In the multiple regression analyses, minutes of non-continuous LTPA remained associated with fetal vagal activity (p<0.05) and the relationships between minutes of non-continuous LTPA and fetal overall HRV (p<0.005) persisted. CONCLUSION These data suggest non-continuous physical activity provides unique benefits to the fetal autonomic nervous system that may give the fetus an adaptive advantage. Further studies are needed to understand the physiological mechanisms and long-term health effects of physical activity (both non-continuous and continuous) performed during pregnancy to both women and their offspring.