Pregnancy Exposure to Perfluoroalkyl Substances and Associations With Prolactin Concentrations and Breastfeeding in the Odense Child Cohort.

CONTEXT: Human exposure to perfluoroalkyl substances (PFAS) has been associated with reduced duration of breastfeeding, although not consistently so, and mechanisms by which PFAS might affect breastfeeding are unknown. OBJECTIVE: To examine the association between early pregnancy serum-PFAS concentrations and breastfeeding termination and to elucidate the potential role of serum-prolactin concentrations in pregnancy. MATERIALS AND METHODS: Pregnant women from the Odense Child Cohort provided blood samples for analysis of 5 major PFAS (n = 1300) and prolactin concentrations (n = 924). They subsequently provided information about the duration of breastfeeding in questionnaires at 3 and 18 months postpartum, and a subgroup also provided breastfeeding information via weekly cell phone text messages. Associations between serum-PFAS concentrations and breastfeeding termination were analyzed using Cox regressions, while linear regression was used to assess associations between serum-PFAS and prolactin concentrations. RESULTS: Increased serum concentrations of perfluorooctane sulfonic acid, perfluorooctanoic acid, perfluorononanoic acid, and ∑PFAS were associated with a 16% (95% CI: 4%-30%), 14% (95% CI: 2%-26%), 14% (95% CI: 3%-27%), and 20% (95% CI: 6%-36%), respectively, increased risk of terminating breastfeeding at any given time after childbirth. Serum-PFAS concentrations were not associated with serum-prolactin concentrations. CONCLUSIONS: These findings are of public health importance due to the global exposures to PFAS. Because breastfeeding is crucial to promote both child health and maternal health, adverse PFAS effects on the ability to breastfeed may have long-term health consequences.

Pregnancy exposure to bisphenol A and duration of breastfeeding.

INTRODUCTION: Bisphenol A (BPA) is frequently used in the production of plastics. It is an endocrine disruptor, and BPA exposure in mice has been associated with reduced offspring growth due to insufficient milk production. However, human studies of associations between BPA exposure and duration of breastfeeding are sparse. METHODS: Pregnant women from the Odense Child Cohort (n = 725) donated a third trimester morning urine sample, which was analyzed for BPA by LC-MS/MS. Information about duration of exclusive and any breastfeeding was obtained through questionnaires three and 18 months postpartum, and a subgroup of women responded to weekly text messages about breastfeeding. Associations between pregnancy BPA exposure and duration of breastfeeding were analyzed using Cox regression adjusting for potential confounders. RESULTS: The median urine BPA concentration was 1.29 ng/mL. Compared to women within the lowest tertile of BPA exposure, women in the second and third tertile were slightly more likely to terminate breastfeeding at any given time; HRs (95% CI) were 1.05 (0.87; 1.26) and 1.06 (0.89; 1.27), respectively, and to terminate exclusive breastfeeding at any time up to 20 weeks after birth, HRs (95% CI) were 1.07 (0.88; 1.28) and 1.06 (0.88; 1.27), respectively. However, confidence intervals were also compatible with no effect or even a protective effect. DISCUSSION: This study indicated that high BPA exposure in pregnancy was associated with shorter duration of breastfeeding. Although our findings were not statistically significant, all estimates were above one suggesting increased risk of early breastfeeding termination with high exposure. Using a single spot morning urine sample to measure BPA has likely caused imprecision as it might not adequately reflect long term exposure. Future studies should consider measuring BPA more than once, including other timepoints during pregnancy and after birth.

Nesfatin-1 in Human Milk and Its Association with Infant Anthropometry.

Breastfed infants have different growth patterns to formula-fed infants and are less likely to develop obesity later in life. Nesfatin-1 is an anorexigenic adipokine that was discovered in human milk more than a decade ago, and its role in infant appetite regulation is not clear. Our aim was to describe nesfatin-1 levels in human milk collected 3-4 months postpartum, associations with infant anthropometry, and factors (maternal pre-pregnancy body mass index (mBMI), high weight gain during pregnancy, milk fat, and energy content) possibly influencing nesfatin-1 levels. We hypothesized that nesfatin-1 levels in mother's milk would differ for infants that were large (high weight-for-age Z-score (WAZ)) or small (low WAZ) at the time of milk sample collection. We used enzyme-linked immunosorbent assay to detect the nesfatin-1 concentration in milk samples from mothers to high WAZ (n = 50) and low WAZ (n = 50) infants. We investigated associations between nesfatin-1 levels and infant anthropometry at 3-4 months of age and growth since birth, using linear regression adjusted for mBMI, birth weight, infant sex, and exclusivity of breastfeeding. We found no difference in nesfatin-1 levels between the two groups and no association with infant anthropometry, even after adjusting for potential confounders. However, high nesfatin-1 levels were correlated with low mBMI. Future research should investigate serum nesfatin-1 level in both mothers, infants and associations with growth in breastfed children.

Breast milk n-3 long-chain polyunsaturated fatty acids and blood pressure: an individual participant meta-analysis.

PURPOSE: It is controversial whether a higher intake of n-3 long-chain polyunsaturated fatty acids (n-3 LC PUFA) through breastfeeding is associated or not to a lower blood pressure (BP) during childhood. We aimed to clarify this point by undertaking a meta-analysis involving the data from seven European birth cohorts. METHODS: We searched https://www.birthcohort.net for studies that had collected breast milk samples, and had at least one BP measurement in childhood. Principal investigators were contacted, and all agreed to share data. One additional study was identified by contacts with the principal investigators. For each cohort, we analyzed the association of breast milk n-3 LC PUFAs with systolic and diastolic BP with linear mixed effects models or linear regression, and pooled the estimates with a random effects model. We also investigated age-specific and sex-specific associations. RESULTS: A total of 2188 participants from 7 cohorts were included. Overall, no associations between breast milk n-3 LC PUFAs and BP were observed. In the pooled analysis, each 0.1 wt% increment in breast milk docosahexaenoic acid (DHA) was associated with a 1.19 (95% CI - 3.31, 0.94) mmHg lower systolic BP. Associations were similar for boys and girls and at different ages. CONCLUSION: In this individual participant meta-analysis, we found no evidence for an association between breast milk n-3 LC PUFAs and BP.

Breastfeeding and Infections in Early Childhood: A Cohort Study.

BACKGROUND: Studies on the association between breastfeeding and infections in children beyond the first year of life reveal conflicting results. In a population-based birth cohort, we investigated whether the duration of breastfeeding was associated with the number of hospitalizations due to infection and symptoms of infection at home. METHODS: In the Odense Child Cohort, text message questionnaires were used to register information on breastfeeding (weekly until end of weaning) and symptoms of infection (biweekly; 12-36 months of age). Hospitalization data were obtained from the Danish National Patient Registry. RESULTS: Of the 1087 invited, 815 mother-infant pairs were included. The median duration of any breastfeeding was 7.6 (interquartile range: 3.5-10.4) months and of exclusive breastfeeding was 2.1 (interquartile range: 0.7-4.4) months. Hospitalization due to infection was seen in 207 (25.4%) infants during the first 3 years of life. The adjusted incidence rate ratio (IRR) for hospitalization due to any infection decreased with a longer duration of any breastfeeding (adjusted IRR: 0.96; 95% confidence interval 0.93-0.99; P < .001). The strongest associations between the duration of any breastfeeding and hospitalizations due to infection were found within the first year of life, for lower respiratory tract infections, and other infections (P ≤ .05). For infants exclusively breastfed, the adjusted IRR for hospitalization was 0.88 (95% confidence interval: 0.80-0.96; P = .006). No protective associations were present between breastfeeding and infection symptoms registered at home from ages 12 to 36 months. CONCLUSIONS: The results suggest that increased duration of breastfeeding, especially exclusive breastfeeding, protects against infections requiring hospitalization in the first year of life but not hospitalizations or symptoms of infection at home beyond the first year.

Long-term monitoring of intracranial pressure in freely-moving rats; impact of different physiological states.

BACKGROUND: Elevated intracranial pressure (ICP) is observed in association with a range of brain disorders. There is limited insight into the regulatory mechanisms of ICP under physiological conditions, and consequently also under pathological conditions. Thereby, to understand the mechanisms underlying ICP dynamics, precise, valid and long-term ICP recordings are of importance in the preclinical setting. Herein, we used a novel telemetric system for ICP recordings which allowed for long-term recordings in freely-moving rats. The aim was to investigate ICP dynamics under different physiological states and investigate how factors such as surgery/recovery, body position, light-dark, co-housing, weight and anesthesia may influence ICP and its waveforms. METHODS: A telemetric device was implanted epidurally in rats and signals were recorded continuously for up to 50 days (n = 14). Recording was divided into three experimental periods: a surgical recovery period (RP), a physiological period (PP) and an experimental period (EP). Histology was performed to study the morphology of implanted rats and non-implanted rats (n = 17). RESULTS: For the first time, we can demonstrate continuous ICP recordings in freely-moving and co-housed rats for up to 50 days with a high degree of stability. The mean ICP in the recording periods were; RP: 3.2 ± 0.6 mmHg, PP: 5.0 ± 0.6 mmHg and EP: 4.7 ± 0.6 mmHg. In the RP, the ICP was significantly lower compared to the PP (P = 0.0034). Significant light-dark difference in ICP with 21% increase in respiratory slow-wave amplitude was observed in the co-housed animals but not in single-housed animals. The ICP signal was raised during the dark period relative to the light (Δ0.3 ± 0.07 mmHg, P = 0.0043). Administration of anesthesia gave a short-term increase in ICP followed by a significant decrease in ICP. No signs of tissue damage or inflammation were found in the implanted brains. CONCLUSIONS: ICP dynamics were influenced by several factors such as, use of anesthesia, light-dark difference and housing conditions. Our study demonstrates the importance of performing ICP physiological measurements in freely-moving animals. This has significant implications for moving the preclinical research field forward in order to properly study ICP physiology during disease development and to explore drug targets for alleviating increased ICP.

Blood Pressure and Angiogenic Markers in Pregnancy: Contributors to Pregnancy-Induced Hypertension and Offspring Cardiovascular Risk.

Pregnancy-induced hypertension is a severe pregnancy complication, increasing risk of long-term cardiovascular disease in mothers and offspring. We hypothesized that maternal blood pressure in pregnancy associated with offspring blood pressure; that the associations were sex-specific; and that maternal circulating placental angiogenic markers (PlGF [placental growth factor] and sFlt-1 [soluble fms-like tyrosine kinase-1]) mediated this relationship. We analyzed data from 2434 women and 2217 children from the Odense Child Cohort, a prospective Danish cohort study. Offspring blood pressure trajectory from 4 months to 5 years was highly associated to maternal first, second, and third trimester blood pressure, and mean blood pressure in pregnancy, independent of maternal and offspring covariates. There were offspring sex-specific associations: Girls from mothers in the highest quartile of first and third trimester blood pressure had significantly higher systolic blood pressure at 5 years than the rest of the cohort (mean difference±SEM: 1.81±0.59 and 2.11±0.59 mm Hg, respectively, all P<0.01); whereas boys had significantly higher diastolic blood pressure at 5 years (mean difference±SEM: 1.11±0.45 and 1.03±0.45, respectively, all P<0.05). Concentrations of PlGF at gestational week 28 correlated inversely to maternal gestational blood pressure trajectory, independent of the diagnosis of pregnancy-induced hypertension, adjusted ß coefficients (95% CI) for predicting systolic blood pressure (SBP): -3.18 (-4.66 to -1.70) mm Hg, for predicting diastolic blood pressure (DBP): -2.48 (-3.57 to -1.40) mm Hg. In conclusion, maternal gestational blood pressure predicted offspring blood pressure trajectory until 5 years in a sex-differential manner. Furthermore, subtle alterations in blood pressure in early pregnancy preceded hypertension or preeclampsia, and PlGF was a mediator of cardiovascular health in pregnancy.

Probiotics in late infancy reduce the incidence of eczema: A randomized controlled trial.

BACKGROUND: Allergic diseases are common and represent a considerable health and economic burden worldwide. We aimed to examine the effect of a combination of two probiotic strains administered in late infancy and early childhood on the development of allergic diseases and sensitization. METHODS: In this double-blind, placebo-controlled intervention trial, participants were randomized to receive a daily mixture of Lactobacillus rhamnosus and Bifidobacterium animalis subsp lactis or placebo-starting prior to attending day care. The intervention period was 6 months, and the parents answered web-based questionnaires on allergic symptoms and doctor's diagnosed allergic disease monthly. IgE was measured at baseline and follow-up. RESULTS: A total of 290 participants were randomized: 144 in the probiotic group and 146 in the placebo group. Mean age at intervention start was 10.1 months. At follow-up (mean age 16.1 months), the incidence of eczema was 4.2% in the probiotic group and 11.5% in the placebo group (P = 0.036). The incidence of asthma and conjunctivitis did not differ between groups, and no children presented with rhinitis. Sensitization was equal in the two groups at intervention start (7.5% and 9.5%, respectively), and two children in each group were sensitized during the intervention. CONCLUSIONS: We observed a significantly lower incidence of eczema in the probiotic group compared to the placebo group. The probiotics were administered in late infancy-prior to attending day care-suggesting a broader window of opportunity using probiotics in the prevention of eczema. The incidence of asthma, rhinitis, conjunctivitis, and sensitization did not differ.

Content of n-3 LC-PUFA in Breast Milk Four Months Postpartum is Associated with Infancy Blood Pressure in Boys and Infancy Blood Lipid Profile in Girls.

Blood pressure (BP) and blood lipid profile (BLP) have been shown to track from childhood into adulthood, and n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) in breast milk have been suggested as mediators of the beneficial long-term effect of breastfeeding on BP and BLP. We aimed to investigate associations between n-3 LC-PUFA content in breast milk at 4 months postpartum and offspring BP and BLP in early life. BP and BLP were measured at 4, 18, and 36 months. Statistical analyses were sex-stratified and adjusted for gestational age, maternal pre-pregnancy body mass index (BMI), and maternal educational level. Based on 336 mother-child dyads, high n-3 LC-PUFA in breast milk was inversely associated with systolic and diastolic BP in boys at 4 months (ß = -20.0 (95% CI = -33.4, -6.7), p = 0.004 and ß = -10.2 (95% CI = -19.8, -0.5), p = 0.039, respectively); inversely associated with HDL cholesterol, and directly associated with triglyceride in girls at 4 months (ß = -0.7 (95% CI = -1.1, -0.3), p = 0.001 and ß = 3.1 (95% CI = 1.0, 5.2), p = 0.005, respectively). Associations observed at the later time points were non-significant. Furthermore, we observed sex-specific changes over time in both size and direction of the associations. Our results indicate that early intake of n-3 LC-PUFA can affect early development in cardiometabolic factors such as BP and BLP in a sex-specific manner. Follow-up and further investigation in later childhood is planned.

Satiety Factors Oleoylethanolamide, Stearoylethanolamide, and Palmitoylethanolamide in Mother's Milk Are Strongly Associated with Infant Weight at Four Months of Age-Data from the Odense Child Cohort.

Regulation of appetite and food intake is partly regulated by N-acylethanolamine lipids oleoylethanolamide (OEA), stearoylethanolamide (SEA), and palmitoylethanolamide (PEA), which induce satiety through endogenous formation in the small intestine upon feeding, but also when orally or systemic administered. OEA, SEA, and PEA are present in human milk, and we hypothesized that the content of OEA, SEA, and PEA in mother's milk differed for infants being heavy (high weight-for-age Z-score (WAZ)) or light (low WAZ) at time of milk sample collection. Ultra-high performance liquid chromatography-mass spectrometry was used to determine the concentration of OEA, SEA, and PEA in milk samples collected four months postpartum from mothers to high (n = 50) or low (n = 50) WAZ infants. Associations between OEA, SEA, and PEA concentration and infant anthropometry at four months of age as well as growth from birth were investigated using linear and logistic regression analyses, adjusted for birth weight, early infant formula supplementation, and maternal pre-pregnancy body mass index. Mean OEA, SEA, and PEA concentrations were lower in the high compared to the low WAZ group (all p < 0.02), and a higher concentration of SEA was associated with lower anthropometric measures, e.g., triceps skinfold thickness (mm) (ß = -2.235, 95% CI = -4.04, -0.43, p = 0.016), and weight gain per day since birth (g) (ß = -8.169, 95% CI = -15.26, -1.08, p = 0.024). This raises the possibility, that the content of satiety factors OEA, SEA, and PEA in human milk may affect infant growth.

Osteopontin Levels in Human Milk Vary Across Countries and Within Lactation Period: Data From a Multicenter Study.

OBJECTIVES: Osteopontin (OPN) is a multifunctional protein expressed in many cell types, tissues and body fluids with the highest concentrations found in milk; significantly higher in human than in bovine milk. Intervention studies have indicated beneficial effects of supplementing infant formula with bovine OPN. In this multicenter study, we determined the OPN content in human milk samples from 629 Chinese, Danish, Japanese and Korean mothers. METHODS: At each study site, milk samples were collected and analyzed for OPN and protein concentration using ELISA and infrared spectroscopy, respectively. RESULTS: A total of 829 milk samples from 629 women were included. When delivering the first sample, mean maternal age was 31.4 years (SD 4.0), and median infant age was 13.4 weeks (interquartile range 4.6-17.9). The median OPN concentration varied across sites; from 99.7 mg/L in Danish, 185.0 mg/L in Japanese, 216.2 mg/L in Korean to 266.2 mg/L in Chinese mothers (P < 0.001), corresponding to 1.3%, 2.4%, 1.8% and 2.7% of the total protein content (OPN/protein%) (P < 0.05), respectively. Based on 75 Chinese and 33 Japanese mothers delivering more than 1 sample, multilevel (mixed model) linear regression analysis showed a decrease in OPN concentration with infant age (ß = (-11.3), 95% confidence interval (CI) = (-13.9) to (-8.8) and ß = (-2.1), 95% CI = (-3.2) to (-0.9), respectively). CONCLUSIONS: In this large multicenter study, we observed statistically significant differences in the OPN concentration and the OPN/protein% in human milk samples between countries. Based on mothers delivering more than 1 sample, a significant decrease within the lactation period was observed.

Breastfeeding, Infant Formula, and Introduction to Complementary Foods-Comparing Data Obtained by Questionnaires and Health Visitors' Reports to Weekly Short Message Service Text Messages.

BACKGROUND: Studies on prevalence and effects of breastfeeding call for reliable and precise data collection to optimize infant nutrition, growth, and health. Data on breastfeeding and infant nutrition are at risk of, for example, recall bias or social desirability bias. OBJECTIVE: The aim of the present analysis was to compare data on infant nutrition, that is, breastfeeding, use of infant formula, and introduction to complementary foods, obtained by four different methods. We assumed that weekly short message service (SMS) questions were the most reliable method, to which the other methods were compared. DESIGN: The study population was part of the Odense Child Cohort. The four methods used were: (a) self-administered questionnaire 3 months postpartum, (b) self-administered questionnaire 18 months postpartum, (c) registrations from health visitors visiting the families several times within the first year of life, and (d) weekly SMS questions introduced shortly after birth. RESULTS: In total, 639 singleton mothers with data from all four methods were included. The proportion of mothers initiating breastfeeding varied from 86% to 97%, the mean duration of exclusive breastfeeding from 12 to 19 weeks, and the mean age when introduced to complementary foods from 19 to 21 weeks. The mean duration of any breastfeeding was 33 weeks across methods. CONCLUSIONS: Compared with the weekly SMS questions, the self-administered questionnaires and the health visitors' reports resulted in a greater proportion of mothers with an unknown breastfeeding status, a longer duration of exclusive breastfeeding and later introduction to complementary foods, while the duration of any breastfeeding did not differ.

Using text messaging to obtain weekly data on infant feeding in a Danish birth cohort resulted in high participation rates.

AIM: Our aim was to use text message questions to obtain prospective, real-time data on exclusive and partial breastfeeding and introduction to complementary foods in a Danish birth cohort. We also wanted to identify factors influencing breastfeeding initiation and cessation. METHODS: This study formed part of the Odense Child Cohort and focused on mothers who gave birth to full-term singletons between April and October 2012. They received the same three to five questions, about breastfeeding, infant formula and introduction to complementary food, three days after birth and then at weekly intervals. RESULTS: We recruited 499 mothers, and the response rate to the first of the weekly questions was ≥89.4% during the study. Three days after birth, 96.7% of mothers were breastfeeding, 61.2% exclusively and 30.2% partially, and 26 weeks after birth 60.2% of mothers were breastfeeding, 1.1% exclusively. Complementary food was introduced at an average age of 20 weeks. Breastfeeding cessation was associated with maternal smoking, lower maternal age and supplementation with infant formula in the first days after birth (all p < 0.05). CONCLUSION: Most mothers initiated breastfeeding, but only 1.1% were exclusively breastfeeding at 26 weeks. Text messaging resulted in high response rates and was a feasible data collection method.

Free Amino Acids in Human Milk and Associations With Maternal Anthropometry and Infant Growth.

OBJECTIVES: Free glutamic acid has an appetite-regulating effect and studies with infant formula have suggested that free amino acids (FAA), especially glutamic acid, can downregulate intake. The content of glutamic acid and glutamine is high in breast milk but varies considerably between mothers. The aim was to investigate whether maternal anthropometry was associated with the content of the FAA glutamic acid or glutamine in breast milk and whether there was a negative association between these FAA and current size or early infant growth in fully breastfed infants. METHODS: From a subgroup of 78 mothers, of which 50 were fully breast feeding, from the Odense Child Cohort breast milk samples were collected 4 months after birth and analyzed for FAA. Information regarding breastfeeding status and infant weight and length was also recorded. RESULTS: There was a large variation in the concentration of the FAAs between mothers. Glutamic acid was positively correlated with mother's prepregnancy weight and height (P ≤ 0.028), but not body mass index. There was no negative correlation between the 2 FAA and infant weight or body mass index. Infant length at 4 months was, however, positively associated with glutamine, (P = 0.013) but the correlation was attenuated when controlling for birth length (P = 0.089). CONCLUSIONS: The hypothesis that a high content of glutamic acid and glutamine in breast milk could downregulate milk intake to a degree affecting early growth could not be confirmed. Maternal factors associated with the level of these FAA in milk and the potential effect on the infant should be investigated further.