Fatty Acid Transfer from Blood to Milk Is Disrupted in Mothers with Low Milk Production, Obesity, and Inflammation.

BACKGROUND: Obesity is associated with chronic inflammation and is a risk factor for insufficient milk production. Inflammation-mediated suppression of LPL could inhibit mammary uptake of long-chain fatty acids (LCFAs; >16 carbons). OBJECTIVES: In an ancillary case-control analysis, we investigated whether women with low milk production despite regular breast emptying have elevated inflammation and disrupted transfer of LCFAs from plasma into milk. METHODS: Data and specimens from a low milk supply study and an exclusively breastfeeding control group were analyzed, with milk production measured by 24-h test-weighing at 2-10 wk postpartum. Low milk supply groups were defined as very low (VL; <300 mL/d; n = 23) or moderate (MOD; ≥300 mL/d; n = 20) milk production, and compared with controls (≥699 mL/d; n = 18). Serum and milk fatty acids (weight% of total) were measured by GC, serum and milk TNF-α by ELISA, and serum high-sensitivity C-reactive protein (hsCRP) by clinical analyzer. Group differences were assessed by linear regression models, chi-square exact tests, and Kruskal-Wallis nonparametric tests. RESULTS: VL cases, as compared with MOD cases and controls, had higher prevalence of elevated serum hsCRP (>5 mg/L; 57%, 15%, and 22%, respectively; P = 0.004), detectable milk TNF-α (67%, 32%, and 33%, respectively; P = 0.04), and obesity (78%, 40%, and 22%, respectively; P = 0.003). VL cases had lower mean ± SD LCFAs in milk (60% ± 3%) than MOD cases (65% ± 4%) and controls (66% ± 5%) (P < 0.001). Milk and serum LCFAs were strongly correlated in controls (r = 0.82, P < 0.001), but not in the MOD (r = 0.25, P = 0.30) or VL (r = 0.20, P = 0.41) groups (Pint < 0.001). CONCLUSIONS: Mothers with very low milk production have significantly higher obesity and inflammatory biomarkers, lower LCFAs in milk, and disrupted association between plasma and milk LCFAs. These data support the hypothesis that inflammation disrupts normal mammary gland fatty acid uptake. Further research should address impacts of inflammation and obesity on mammary fatty acid uptake for milk production.

Measures of Maternal Metabolic Health as Predictors of Severely Low Milk Production.

Background: A comprehensive approach to breastfeeding support requires elucidation of how metabolic health influences milk production. Objective: We compared metabolic health indicators in women with severely low milk output versus those with moderate/normal milk output using a case-control study design, with nested and external control groups. Design: Cases and nested controls were derived from women screened for a low milk supply trial, with cases defined as severely low milk output (<300 mL/24 hours), and nested controls defined as moderate/normal milk output (>300 mL/24 hours). In addition, we included an external control group of exclusively breastfeeding women. All were enrolled at 2-10 weeks postdelivery of a healthy term infant. Milk output and breast emptying frequency were recorded through test-weigh. Metabolic health variables included all components of the metabolic syndrome, homeostatic model assessment of insulin resistance (HOMA-IR), and diagnosis of gestational diabetes mellitus (GDM). Results: Maximum milk output, mL/24 hours, ranged as follows: 30-281 in cases (n = 18), 372-801 in nested controls (n = 12), and 661-915 in external controls (n = 12). Mean breast emptying frequency in cases was not significantly different from nested or external controls. All metabolic syndrome components and HOMA-IR were significantly worse in cases as compared with both nested and external control groups (p < 0.05). There was no significant difference between the nested and external control groups for these variables. GDM prevalence was 39%, 0%, and 8%, across cases, nested control, and external control groups, respectively (chi-square p-value = 0.02). Conclusion: Results from this small case-control study identify class 2+ obesity and poor metabolic health as strong risk factors for severely low milk production. These findings should be further validated in larger prospective cohort studies designed to identify individuals at risk for metabolically driven low milk supply. In addition, clinical and qualitative research studies aimed at improving patient-centered approaches to the management of persistent low milk supply are needed.

Validity of a 3-Hour Breast Milk Expression Protocol in Estimating Current Maternal Milk Production Capacity and Infant Breast Milk Intake in Exclusively Breastfeeding Dyads.

Objective: An efficient method for measuring maternal milk production is needed. Our objectives were to: (1) validate a milk production rate (MPR) protocol in exclusively breastfeeding mothers; (2) determine MPR change following 48 hours of increased breast emptying; (3) assess agreement between MPR and infant test-weighing; and (4) characterize MPR in early postpartum exclusively breastfeeding mothers. Materials and Methods:N = 23 mothers emptied both breasts hourly over 3 hours (h0, h1, h2, and h3). We estimated steady-state MPR as mean (h2 and h3). Subset A mothers (n = 5) also completed MPR measurements after 48 hours of increased breast emptying. Subset B mothers (n = 16) also test-weighed for 48 hours. We used paired t-test to examine within-participant change in hourly milk yield and MPR; and we used Bland-Altman analysis to compare 24-hour milk production (g/24 hours) measured using test-weight versus MPR. Results are reported as mean ± standard deviation or (±95% limits of agreement). Results: Mothers were 54 ± 14 days postpartum. Paired difference in h3-h2 hourly milk yield was not significantly different (p > 0.05, 3 ± 10 g/hour). In Subset A (n = 5), MPR declined from 50 ± 13 to 43 ± 16 g/hour (p = 0.003) following 48 hours of increased breast emptying. In Study B (n = 16), mean infant test-weighed intake (TW) was 717 ± 119 g/24 hours, and mean MPR was 1,085 ± 300 g/24 hours. Mean difference (MPR-test-weigh) and mean ratio (MPR/test-weigh) significantly increased as MPR increased (p < 0.05). For infants with adequate weight gain (>20 g/24 hours, n = 12), mean MPR = 48 ± 12 g/hour (range, 35-78 g/hour). Conclusion: MPR is a valid measure of current maternal milk production capacity, but is not accurate for evaluating infant intake in exclusively breastfeeding dyads.

The Relation between Breast Milk Sodium to Potassium Ratio and Maternal Report of a Milk Supply Concern.

We report that, among exclusively breastfeeding mothers at day 7 postpartum, those with milk supply concerns were significantly more likely to exhibit biochemical evidence of less progress toward mature lactation (elevated ratio of breast milk sodium to potassium concentration). Furthermore, an elevated ratio of breast milk sodium to potassium concentration was predictive of early weaning.

Systems biology evaluation of cell-free amniotic fluid transcriptome of term and preterm infants to detect fetal maturity.

BACKGROUND: Amniotic fluid (AF) is a proximal fluid to the fetus containing higher amounts of cell-free fetal RNA/DNA than maternal serum, thereby making it a promising source for identifying novel biomarkers that predict fetal development and organ maturation. Our aim was to compare AF transcriptomic profiles at different time points in pregnancy to demonstrate unique genetic signatures that would serve as potential biomarkers indicative of fetal maturation. METHODS: We isolated AF RNA from 16 women at different time points in pregnancy: 4 from 18 to 24 weeks, 6 from 34 to 36 weeks, and 6 from 39 to 40 weeks. RNA-sequencing was performed on cell-free RNA. Gene expression and splicing analyses were performed in conjunction with cell-type and pathway predictions. RESULTS: Sample-level analysis at different time points in pregnancy demonstrated a strong correlation with cell types found in the intrauterine environment and fetal respiratory, digestive and external barrier tissues of the fetus, using high-confidence cellular molecular markers. While some RNAs and splice variants were present throughout pregnancy, many transcripts were uniquely expressed at different time points in pregnancy and associated with distinct neonatal co-morbidities (respiratory distress and gavage feeding), indicating fetal immaturity. CONCLUSION: The AF transcriptome exhibits unique cell/organ-selective expression patterns at different time points in pregnancy that can potentially identify fetal organ maturity and predict neonatal morbidity. Developing novel biomarkers indicative of the maturation of multiple organ systems can improve upon our current methods of fetal maturity testing which focus solely on the lung, and will better inform obstetrical decisions regarding delivery timing.

In-hospital formula use increases early breastfeeding cessation among first-time mothers intending to exclusively breastfeed.

OBJECTIVE: To evaluate in-hospital formula supplementation among first-time mothers who intended to exclusively breastfeed and determined if in-hospital formula supplementation shortens breastfeeding duration after adjusting for breastfeeding intention. STUDY DESIGN: We assessed strength of breastfeeding intentions prenatally in a diverse cohort of expectant primiparae and followed infant feeding practices through day 60. Among mothers planning to exclusively breastfeed their healthy term infants for ≥1 week, we determined predictors, reasons, and characteristics of in-hospital formula supplementation, and calculated the intention-adjusted relative risk (ARR) of not fully breastfeeding days 30-60 and breastfeeding cessation by day 60 with in-hospital formula supplementation (n = 393). RESULTS: Two hundred ten (53%) infants were exclusively breastfed during the maternity stay and 183 (47%) received in-hospital formula supplementation. The most prevalent reasons mothers cited for in-hospital formula supplementation were: perceived insufficient milk supply (18%), signs of inadequate intake (16%), and poor latch or breastfeeding (14%). Prevalence of not fully breastfeeding days 30-60 was 67.8% vs. 36.7%, ARR 1.8 (95% CI, 1.4-2.3), in-hospital formula supplementation vs exclusively breastfed groups, respectively, and breastfeeding cessation by day 60 was 32.8% vs. 10.5%, ARR 2.7 (95% CI, 1.7-4.5). Odds of both adverse outcomes increased with more in-hospital formula supplementation feeds (not fully breastfeeding days 30-60, P = .003 and breastfeeding cessation, P = .011). CONCLUSIONS: Among women intending to exclusively breastfeed, in-hospital formula supplementation was associated with a nearly 2-fold greater risk of not fully breastfeeding days 30-60 and a nearly 3-fold risk of breastfeeding cessation by day 60, even after adjusting for strength of breastfeeding intentions. Strategies should be sought to avoid unnecessary in-hospital formula supplementation and to support breastfeeding when in-hospital formula supplementation is unavoidable.

Breastfeeding concerns at 3 and 7 days postpartum and feeding status at 2 months.

OBJECTIVE: We characterized breastfeeding concerns from open-text maternal responses and determined their association with stopping breastfeeding by 60 days (stopping breastfeeding) and feeding any formula between 30 and 60 days (formula use). METHODS: We assessed breastfeeding support, intentions, and concerns in 532 expectant primiparas and conducted follow-up interviews at 0, 3, 7, 14, 30, and 60 days postpartum. We calculated adjusted relative risk (ARR) and adjusted population attributable risk (PAR) for feeding outcomes by concern category and day, adjusted for feeding intentions and education. RESULTS: In 2946 interviews, 4179 breastfeeding concerns were reported, comprising 49 subcategories and 9 main categories. Ninety-two percent of participants reported ≥ 1 concern at day 3, with the most predominant being difficulty with infant feeding at breast (52%), breastfeeding pain (44%), and milk quantity (40%). Concerns at any postpartum interview were significantly associated with increased risk of stopping breastfeeding and formula use, with peak ARR at day 3 (eg, stopping breastfeeding ARR [95% confidence interval] = 9.2 [3.0-infinity]). The concerns yielding the largest adjusted PAR for stopping breastfeeding were day 7 "infant feeding difficulty" (adjusted PAR = 32%) and day 14 "milk quantity" (adjusted PAR = 23%). CONCLUSIONS: Breastfeeding concerns are highly prevalent and associated with stopping breastfeeding. Priority should be given to developing strategies for lowering the overall occurrence of breastfeeding concerns and resolving, in particular, infant feeding and milk quantity concerns occurring within the first 14 days postpartum.

Short-term exposure to a high-protein diet differentially affects glomerular filtration rate but not Acid-base balance in older compared to younger adults.

There is conflicting evidence regarding the effects of high protein intake on kidney health, especially as it relates to age. We investigated the short-term effects of a high-protein diet on kidney function and systemic acid-base homeostasis in older compared to younger adults. The subjects were healthy men and women either between the ages of 25 and 40 years (n=12) or 55 and 70 years (n=10). They underwent a two-period crossover trial with each period consisting of 2 weeks of usual diet followed by a 1-week experimental diet. During the experimental diet period subjects consumed metabolic meals that provided either low protein content (0.5 g protein/kg/day) or high protein content (2.0 g protein/kg/day). Outcome measures included blood and urine markers of renal function and acid-base balance. An analysis of variance was used to assess differences between age groups with respect to experimental diet. The older group, mainly women, showed an increase in glomerular filtration rate after the high-protein compared to low-protein diet; the younger group did not. Urinary pH was significantly lower, and ammonium excretion was significantly higher after the high-protein diet in both age groups, but neither group developed a clinically detectable acidosis after the week of receiving a high-protein diet.