Reaction times, learning, and executive functioning in adults born preterm.

BACKGROUND: This study examines cognitive functioning in adults born across the range of prematurity with appropriate or small for gestational age (SGA) birth weight compared with full-term controls. METHODS: ESTER Preterm Birth Study participants without severe disabilities, comprising 133 early preterm (<34 weeks, 17% SGA), 241 late preterm (34 + 0-36 + 6 weeks, 13% SGA), and 348 full-term subjects, performed the Cogstate® test at a mean age of 23.3 (SD = 1.2) years. Subtests measured paired associate learning, psychomotor function, executive function, spatial memory efficiency, visual memory, attention, working memory, visual learning, and emotional cognition. Data were analyzed with linear regression, full models adjusted for prenatal and postnatal factors and socioeconomic position. RESULTS: Early preterm, late preterm, and full-term participants showed similar abilities in almost all subtests. Early preterm participants had 0.6 fewer moves/10 s (95% CI: -1.0; -0.2, full model) and late preterm and SGA participants had 1.3 fewer moves/10 s (95% CI: -2.1; -0.4) than full-term controls in the Groton Maze Learning Test, indicating weaker spatial memory efficiency. CONCLUSIONS: Adults born across the range of prematurity on average lack major defects in cognitive abilities. Cognitive problems may persist to adulthood only among those born the smallest: very preterm or preterm and SGA. IMPACT: Although preterm birth is a risk for the developing brain, adults born preterm as a group showed similar cognitive performance to their full-term peers. Children born preterm across gestational ages show defects in cognitive domains. With a supportive environment, many of them have the potential to catch up with those born at term. The unfavorable effect of late preterm birth on cognitive functions in childhood may not persist to adulthood; in this study, adults born late preterm showed similar cognitive functioning to adults born full-term. The deficits in cognitive function in adults born preterm detected by earlier studies mainly concern those born the smallest, i.e., very preterm or preterm and small for gestational age.

Cardiac Autonomic Function in Adults Born Preterm.

OBJECTIVE: To evaluate cardiac autonomic function in adults born preterm. STUDY DESIGN: We studied the association between prematurity and cardiac autonomic function using heart rate variability measurements in 600 adults (mean age of 23.3 years) from a geographically based cohort in Northern Finland. There were 117 young adults born early preterm (<34 weeks), 207 born late preterm (34-36 weeks), and 276 born at term (≥37 weeks, controls). Autonomic function was analyzed by calculating time and frequency domain heart rate variability measurements using linear regression. RESULTS: Compared with controls, the mean difference in root mean square of successive differences (indicating cardiac vagal activity) was -12.0% (95% CI -22.2%, -0.5%, adjusted for sex, age, source cohort, and season P = .04) for the early preterm group and -7.8% (-16.8%, 2.0%, P = .12) for the late preterm group. Mean differences with controls in low frequency power (indicating cardiac vagal activity, including some sympathetic- and baroreflex-mediated effects) were -13.6% (-26.7%, 1.8%, P = .08) for the early preterm group and -16.4% (-27.0%, -4.3%, P = .01) for the late preterm group. Mean differences in high frequency power (quantifying cardiac vagal modulation in respiratory frequency) were -19.2% (-36.6%, 2.9%, P = .09) for the early preterm group and -13.8% (-29.4%, 5.3%, P = .15) for the late preterm group. Differences were attenuated when controlled for body mass index and physical activity. CONCLUSIONS: Our results suggest altered autonomic regulatory control in adults born preterm, including those born late preterm. Altered autonomic regulatory control may contribute to increased cardiovascular risk in adults born preterm.

Postexercise Heart Rate Recovery in Adults Born Preterm.

OBJECTIVE: To evaluate postexercise heart rate recovery (HRR) in adults born preterm. STUDY DESIGN: We studied the association between preterm birth and postexercise HRR in 545 adults (267 women) at 23.3 years of age (range 19.9-26.3 years). One hundred three participants were born early preterm (<34 completed weeks), 178 late preterm (34-36), and 264 were full term (control group). HRR was calculated as change in heart rate (HR) 30 seconds and 60 seconds after cessation of submaximal step test and maximum HR slope during the first minute after. RESULTS: Mean peak HR was 159.5 bpm in the early preterm (P = .16 with controls), 157.8 bpm in the late preterm (P = .56), and 157.0 bpm in the control group. Mean HRR 30 seconds after exercise was 3.2 bpm (95% CI 1.1-5.2) lower in the early preterm group and 2.1 bpm (0.3-3.8) lower in the late preterm group than the full term controls. Mean 60s HRR was 2.5 (-0.1 to 5.1) lower in the early preterm group and 2.8 bpm (0.6-4.9) lower in the late preterm group. Mean maximum slope after exercise was 0.10 beats/s (0.02-0.17) lower in the early preterm group and 0.06 beats/s (0.00-0.12) lower in the late preterm group. CONCLUSIONS: Our results suggest reduced HRR after exercise in adults born preterm, including those born late preterm. This suggests altered reactivation of the parasympathetic nervous system, which may contribute to cardiovascular risk among adults born preterm.

Maternal pre-pregnancy overweight and gestational diabetes and dietary intakes among young adult offspring.

BACKGROUND/OBJECTIVES: Maternal pre-pregnancy overweight/obesity and gestational diabetes (GDM) are associated with increased fat deposition in adult offspring. The purpose of this study was to identify if maternal pre-pregnancy overweight (body mass index (BMI) ≥ 25 kg/m2) or GDM are associated with dietary quality or intake in adult offspring. SUBJECTS/METHODS: Participants (n = 882) from two longitudinal cohort studies (ESTER Maternal Pregnancy Disorders Study and the Arvo Ylppö Longitudinal Study) completed a validated food-frequency questionnaire at a mean age of 24.2 years (SD 1.3). Diet quality was evaluated by a Recommended Finnish Diet Index (RDI). The study sample included offspring of normoglycaemic mothers with pre-pregnancy overweight/obesity (ONO = 155), offspring of mothers with GDM regardless of BMI (OGDM = 190) and offspring of mothers with normal weight and no GDM (controls; n = 537). RESULTS: Among men, daily energy and macronutrient intakes were similar in ONO and controls. However, after adjusting for current offspring characteristics, including BMI, daily carbohydrate intake relative to total energy intake was higher in ONO-men [2.2 percentages of total energy intake (95% confidence interval 0.4, 4.0)]. In ONO-women, macronutrient intakes relative to total energy intake were similar with controls, while total daily energy intake seemed lower [-587.2 kJ/day (-1192.0, 4.4)]. After adjusting for confounders, this difference was attenuated. Adherence to a healthy diet, as measured by RDI, was similar in ONO and controls [mean difference: men 0.40 (-0.38, 1.18); women 0.25 (-0.50, 1.00)]. In OGDM vs. controls, total energy and macronutrient intakes were similar for both men and women. Also adherence to a healthy diet was similar [RDI: men 0.09 (-0.62, 0.80); women -0.17 (-0.93, 0.59)]. CONCLUSIONS: Our study suggested higher daily carbohydrate intake in male offspring exposed to maternal pre-pregnancy overweight/obesity, compared with controls. Prenatal exposure to GDM was not associated with adult offspring dietary intakes.

Gestational Diabetes But Not Prepregnancy Overweight Predicts for Cardiometabolic Markers in Offspring Twenty Years Later.

CONTEXT: Maternal gestational diabetes mellitus (GDM) and prepregnancy overweight/obesity [body mass index (BMI) ≥25 kg/m2] might adversely affect offspring cardiometabolic health. OBJECTIVE: To assess the associations between maternal GDM and prepregnancy overweight/obesity with adult offspring cardiometabolic risk factors. DESIGN: Longitudinal cohort study (ESTER Maternal Pregnancy Disorders Study and the Arvo Ylppö Longitudinal Study). SETTING: Province of Uusimaa and Northern Finland. PARTICIPANTS: At a mean age of 24.1 ± 1.3 years, we classified offspring as offspring of mothers with GDM regardless of the prepregnancy BMI (OGDM; n = 193); normoglycemic mothers with prepregnancy overweight/obesity (ONO; n = 157); and normoglycemic mothers with prepregnancy BMI <25 kg/m2 (controls; n = 556). MAIN OUTCOME MEASURES: We assessed the cardiometabolic biomarkers from blood and measured the blood pressure at rest and heart rate. RESULTS: Compared with the controls, the OGDM and ONO groups had greater fasting glucose (1.6%; 95% CI, 0.1% to 3.1%; and 2.3%; 95% CI, 0.5% to 4.3%, respectively) and insulin (12.7%; 95% CI, 4.4% to 21.9%; and 8.7%; 95% CI, 0.2% to 17.8%). These differences attenuated to nonsignificance when adjusted for confounders and/or current offspring characteristics, including BMI or body fat percentage. The OGDM group had lower SHBG (men, -12.4%; 95% CI, -20.2% to -3.9%; women, -33.2%; 95% CI, -46.3% to -16.8%), high-density lipoprotein (-6.6%; 95% CI, -10.9% to -2.2%), and apolipoprotein A1 (-4.5%; 95% CI, -7.5% to -1.4%). These differences survived the adjustments. The heart rate and other biomarkers were similar among the groups. CONCLUSIONS: Adult offspring of mothers with GDM have increased markers of insulin resistance and a more atherogenic lipid profile. These were only partly explained by confounders or current offspring adiposity. Maternal prepregnancy overweight/obesity was associated with impaired offspring glucose regulation, which was explained by confounders and/or current adiposity.

Alpha-lactorphin and beta-lactorphin improve arterial function in spontaneously hypertensive rats.

alpha-lactorphin (Tyr-Gly-Leu-Phe) lowers blood pressure in conscious adult SHR. This tetrapeptide is originally released from milk protein alpha-lactalbumin by enzymatic hydrolysis. In order to evaluate the antihypertensive mechanisms of alpha-lactorphin, the effects of the tetrapeptide on vascular function were investigated in (30-35 weeks old) spontaneously hypertensive rats (SHR) with established hypertension and age-matched normotensive Wistar-Kyoto (WKY) rats in vitro. In addition, we studied the vascular effects of another structurally related tetrapeptide, beta-lactorphin (Tyr-Leu-Leu-Phe), which originates from milk protein beta-lactoglobulin. Endothelium-dependent relaxation to acetylcholine (ACh) was reduced in mesenteric arterial preparations of SHR as compared to those of WKY. In SHR, the ACh-induced relaxation was augmented by alpha-lactorphin or beta-lactorphin. The role of nitric oxide (NO) is suggested, since this improvement was abolished by the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). Simultaneous potassium channel inhibitor tetraethylammonium (TEA) elicited no additional effect on the ACh-induced relaxation. The cyclooxygenase inhibitor diclofenac did not attenuate the augmented ACh relaxation induced by alpha-lactorphin or beta-lactorphin, suggesting that endothelial vasodilatory prostanoids were not involved in the effect of the tetrapeptides. Endothelium-independent relaxation to the NO donor sodium nitroprusside (SNP) was augmented in mesenteric arterial preparations of SHR by simultaneous beta-lactorphin. The tetrapeptides did not alter vascular responses in mesenteric arteries from WKY. In conclusion, both alpha-lactorphin and beta-lactorphin improved vascular relaxation in adult SHR in vitro. The beneficial effect of alpha-lactorphin was directed towards endothelial function, whereas beta-lactorphin also enhanced endothelium-independent relaxation.

Effect of long-term intake of milk products on blood pressure in hypertensive rats.

The effect of long-term intake of two fermented milk products on the development of hypertension was compared in young spontaneously hypertensive rats (SHR). The products contained tripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), which have been shown to possess angiotensin converting enzyme (ACE) inhibitory activity. Six-week-old SHR were divided into four groups to receive orally ad libitum water, skim milk or two fermented milk poducts (fermented milk A or fermented milk B; the latter is commercially available in Japan with trade name Calpis) for 14 weeks. The calculated intake of IPP was 0.4 mg/d and 0.2 mg/d in the groups receiving fermented milk A and B, respectively, whereas the corresponding amounts for VPP were 0.6 mg/d and 0.3 mg/d. Systolic blood pressure (SBP) was monitored weekly by tail-cuff method. The development of hypertension was significantly attenuated in both groups receiving fermented milk products, whereas skim milk did not affect blood pressure. The effect was detectable after 6 weeks of treatment. At the end of the experiment, the lowest blood pressure level was found in the group receiving fermented milk A: the SBP was 21 mm Hg lower than in the group receiving water and 10 mm Hg lower than in the group receiving fermented milk B. This difference could be explained by larger intake of ACE inhibitory tripeptides in the group receiving fermented milk A as compared with fermented milk B.