Human milk insulin is related to maternal plasma insulin and BMI: but other components of human milk do not differ by BMI.

BACKGROUND/OBJECTIVES: The impact of maternal BMI and insulin sensitivity on bioactive components of human milk (HM) is not well understood. As the prevalence of obesity and diabetes rises, it is increasingly critical that we understand how maternal BMI and hormones associated with metabolic disease relate to concentrations of bioactive components in HM. SUBJECTS/METHODS: This longitudinal cohort design followed 48 breastfeeding mothers through the first four months of lactation, collecting fasting morning HM samples at 2-weeks and 1, 2, 3 and 4-months, and fasting maternal blood at 2-weeks and 4-months. Insulin, glucose, adipokines leptin and adiponectin, appetite regulating hormone ghrelin, marker of oxidative stress 8OHdG and inflammatory cytokines (IL-6, IL-8, and TNF-a) were measured in HM and maternal plasma. RESULTS: A total of 26 normal weight (NW) (BMI=21.4±2.0 kg/m2) and 22 overweight/obese (OW/Ob) (BMI=30.4±4.2 kg/m2) were followed. Of all HM analytes measured, only insulin and leptin were different between groups - consistently higher in the OW/Ob group (leptin: P<0.001; insulin: P<0.03). HM insulin was 98% higher than maternal plasma insulin at 2-weeks and 32% higher at 4-months (P<0.001). Maternal fasting plasma insulin and HOMA-IR were positively related to HM insulin at 2-weeks (P<0.001, R2⩾0.38, n=31), and 4-months (P⩽0.005, R2⩾0.20, n=38). CONCLUSIONS: The concentrations of insulin in HM are higher than in maternal plasma and are related to maternal BMI and insulin sensitivity. With the exception of leptin, there were minimal other differences observed in HM composition across a wide range in maternal BMI.

Early infant adipose deposition is positively associated with the n-6 to n-3 fatty acid ratio in human milk independent of maternal BMI.

BACKGROUND/OBJECTIVES: Excessive infant weight gain in the first 6-month of life is a powerful predictor of childhood obesity and related health risks. In mice, omega-6 fatty acids (FAs) serve as potent ligands driving adipogenesis during early development. The ratio of omega-6 relative to omega-3 (n-6/n-3) FA in human milk (HM) has increased threefold over the last 30 years, but the impact of this shift on infant adipose development remains undetermined. This study investigated how maternal obesity and maternal dietary FA (as reflected in maternal red blood cells (RBCs) composition) influenced HM n-6 and n-3 FAs, and whether the HM n-6/n-3 ratio was associated with changes in infant adipose deposition between 2 weeks and 4 months postpartum. SUBJECTS/METHODS: Forty-eight infants from normal weight (NW), overweight (OW) and obese (OB) mothers were exclusively or predominantly breastfed over the first 4 months of lactation. Mid-feed HM and maternal RBC were collected at either transitional (2 weeks) or established (4 months) lactation, along with infant body composition assessed using air-displacement plethysmography. The FA composition of HM and maternal RBC was measured quantitatively by lipid mass spectrometry. RESULTS: In transitional and established HM, docosahexaenoic acid (DHA) was lower (P=0.008; 0.005) and the arachidonic acid (AA)/DHA+eicosapentaenoic acid (EPA) ratio was higher (P=0.05; 0.02) in the OB relative to the NW group. Maternal prepregnancy body mass index (BMI) and AA/DHA+EPA ratios in transitional and established HM were moderately correlated (P=0.018; 0.001). Total infant fat mass was increased in the upper AA/DHA+EPA tertile of established HM relative to the lower tertile (P=0.019). The amount of changes in infant fat mass and percentage of body fat were predicted by AA/EPA+DHA ratios in established HM (P=0.038; 0.010). CONCLUSIONS: Perinatal infant exposures to a high AA/EPA+DHA ratio during the first 4 months of life, which is primarily reflective of maternal dietary FA, may significantly contribute to the way infants accumulate adipose.

Maternal diet quality in pregnancy and neonatal adiposity: the Healthy Start Study.

BACKGROUND/OBJECTIVES: Poor maternal diet in pregnancy can influence fetal growth and development. We tested the hypothesis that poor maternal diet quality during pregnancy would increase neonatal adiposity (percent fat mass (%FM)) at birth by increasing the fat mass (FM) component of neonatal body composition. METHODS: Our analysis was conducted using a prebirth observational cohort of 1079 mother-offspring pairs. Pregnancy diet was assessed via repeated Automated Self-Administered 24-h dietary recalls, from which Healthy Eating Index-2010 (HEI-2010) scores were calculated for each mother. HEI-2010 was dichotomized into scores of ⩽57 and >57, with low scores representing poorer diet quality. Neonatal %FM was assessed within 72 h after birth with air displacement plethysmography. Using univariate and multivariate linear models, we analyzed the relationship between maternal diet quality and neonatal %FM, FM, and fat-free mass (FFM) while adjusting for prepregnancy body mass index (BMI), physical activity, maternal age, smoking, energy intake, preeclampsia, hypertension, infant sex and gestational age. RESULTS: Total HEI-2010 score ranged between 18.2 and 89.5 (mean: 54.2, s.d.: 13.6). An HEI-2010 score of ⩽57 was significantly associated with higher neonatal %FM (ß=0.58, 95% confidence interval (CI) 0.07-1.1, P<0.05) and FM (ß=20.74; 95% CI 1.49-40.0; P<0.05) but no difference in FFM. CONCLUSIONS: Poor diet quality during pregnancy increases neonatal adiposity independent of maternal prepregnancy BMI and total caloric intake. This further implicates maternal diet as a potentially important exposure for fetal adiposity.

Striking differences in estimates of infant adiposity by new and old DXA software, PEAPOD and skin-folds at 2 weeks and 1 year of life.

BACKGROUND: Infant adiposity better predicts childhood obesity/metabolic risk than weight, but technical challenges fuel controversy over the accuracy of adiposity estimates. OBJECTIVE: We prospectively measured adiposity (%fat) in term newborns (NB) at 2 weeks (n = 41) and 1 year (n = 30). METHODS: %fat was measured by dual X-ray absorptiometry (DXA), PEAPOD and skin-folds (SF). DXAs were analyzed using Hologic Apex software 3.2(DXAv1) and a new version 5.5.2(DXAv2). RESULTS: NB %fat by DXAv2 was 55% higher than DXAv1 (14.2% vs. 9.1%), 45% higher than SF (9.8%), and 36% higher than PEAPOD (10.4%). Among NB, Pearson correlations were 0.73-0.89, but agreement (intra-class correlations) poor between DXAv2 and DXAv1 (0.527), SF (0.354) and PEAPOD (0.618). At 1 year, %fat by DXAv2 was 51% higher than DXAv1 (33.6% vs. 22.4%), and twice as high compared with SF (14.6%). Agreement was poor between DXAv2 and DXAv1 (0.204), and SF (0.038). The absolute increase in %fat from 2 weeks to 1 year was 19.7% (DXAv2), 13.6% (DXAv1) and only 4.8% by SF. CONCLUSION: Analysis of the same DXA scans using new software yielded considerably higher adiposity estimates at birth and 1 year compared with the previous version. Using different modalities to assess body composition longitudinally is problematic. Standardization is gravely needed to determine how early life exposures affect childhood obesity/metabolic risk.

Current concepts of anticoagulant therapy in pregnancy.

The optimal use of anticoagulants during pregnancy will continue to be controversial until appropriate randomized controlled and prospective trials with adequate sample sizes are completed. The relative low frequency of thromboembolic events, the concerns about maternal and fetal safety of both treatment and withholding treatment, and the reservations about prospectively enrolling pregnant women in treatment trials has sadly dissuaded the appropriate study of this life-threatening condition. North American trials that enroll pregnant women to evaluate the efficacy of LMWH are of preeminent importance owing to their superior bioavailability, ease in dosing, longer half-life, and side effect profile. Similarly, trials evaluating the optimal management of women of childbearing age with valvular disease are critical to reduce the considerable maternal and fetal morbidity and mortality associated with these pregnancies. Such definitive studies will need to be multicenter in design and it is hoped that the National Institutes of Health initiative to enroll pregnant women in clinical trials will at last be realized in the near future.

Comparison of protein S functional and antigenic assays in normal pregnancy.

OBJECTIVE: Our purpose was to determine the effect of pregnancy on the protein S functional assay (clot based), which is used to screen for all subtypes of protein S deficiency states, and to compare its behavior in pregnancy with antigenic assays. STUDY DESIGN: This was a cross-sectional study of 37 normal pregnant women without thromboembolic risks who were tested by both functional and antigenic protein S assays during the first, second, and third trimesters. RESULTS: Mean protein S functional levels decline strikingly from the first to the third trimester, all 10 third-trimester patients had functional protein S levels well below the lower limit of the reference range. In contrast, only 3 of 10 third-trimester and none of the second-trimester patients had free protein S antigenic levels below the reference range. CONCLUSIONS: The protein S functional assay should not be used in pregnancy to screen for the subtypes of protein S deficiency; misdiagnosis and inappropriate treatment could result.

Heparin levels to guide thromboembolism prophylaxis during pregnancy.

OBJECTIVE: Our purpose was to determine the dose of heparin required in pregnant women to achieve the same heparin levels as standard doses of 5000 units given subcutaneously every 12 hours in the nonpregnant population. STUDY DESIGN: Fourteen pregnant women placed on heparin prophylaxis for a history of thromboembolism had blood drawn for 64 anti-Xa level determinations in the second and third trimesters. Heparin doses were adjusted in an attempt to achieve a midinterval or peak level of 0.05 to 0.25 U/ml, which corresponds to the range seen in nonpregnant patients given standard doses of 5000 units subcutaneously every 12 hours. RESULTS: A standard heparin dose of 5000 units given subcutaneously every 12 hours was inadequate to achieve the desired range in this pregnant population. In five of nine second-trimester pregnancies 7500 units given subcutaneously every 12 hours was inadequate to attain this range. In six of 13 third-trimester pregnancies, > 10,000 units subcutaneously every 12 hours was needed. CONCLUSIONS: Heparin requirements may increase and are highly variable in patients during pregnancy. Until appropriate clinical outcomes trials can determine optimal dosing, measuring anti-Xa activity may be useful to guide therapy.

Controversies in thromboembolic disease during pregnancy: a critical review.

OBJECTIVE: To critically appraise the body of literature concerning strategies for the prevention of thromboembolism during pregnancy. DATA SOURCES: We used the Medline data base and reference lists of articles to identify all English-language papers examining thromboembolism during pregnancy. METHODS OF STUDY SELECTION: We identified 156 articles in the obstetric literature and 29 articles in the medical literature that referenced nonpregnant populations. Together, these articles form the primary data base on which most recommendations are based. DATA EXTRACTION AND SYNTHESIS: There are no level 1 trials (large randomized trials with definitive results) in the obstetric literature examining the efficacy of thromboembolism prophylaxis during pregnancy. There are only two level 2 trials (small randomized trials with uncertain results because of moderate to high alpha or beta error) that address prophylactic strategies in pregnant women with histories of thromboembolism or the antiphospholipid antibody syndrome. The remainder of the published trials are observational, some prospective but predominantly retrospective. Many of the recommendations from consensus panels regarding prophylactic strategies in pregnancy were based on level 1 trials in nonpregnant populations. CONCLUSION: Although women with a history of thromboembolic disease are at appreciable risk of recurrence during pregnancy, the exact incidence is unknown and there are no adequate efficacy trials demonstrating that prophylactic regimens are effective. Heparin is the anticoagulant of choice in pregnancy; however, changes in metabolism and clearance make adequate dosing problematic. Expert consensus panels disagree over the optimal management of pregnant women at risk for thromboembolism. Randomized controlled trials during pregnancy are needed if any progress is to be made in combating this lethal disorder.

Heparin-induced thrombocytopenia and thrombosis: a case study and clinical overview.

PURPOSE/OBJECTIVES: To describe the mechanisms and nursing care associated with heparin-induced thrombocytopenia and thrombosis (HITT). DATA SOURCES: Published books and journal articles as well as clinical experience. DATA SYNTHESIS: HITT is an immune reaction that occurs in 1%-10% of individuals receiving heparin therapy. Characterized by a sudden drop in platelets, it can result in life-threatening hemorrhage and thrombus-related events. CONCLUSIONS: Heparin commonly is used in many oncology treatment settings. Awareness of this potentially serious complication and knowledge of its treatment is critical to safe administration. IMPLICATIONS FOR NURSING PRACTICE: Astute assessment skills are the key to diagnosis and treatment of HITT.

A prospective study of heparin-induced osteoporosis in pregnancy using bone densitometry.

OBJECTIVE: Our purpose was to evaluate the subclinical occurrence of heparin-induced osteoporosis in pregnancy, by means of bone densitometry. STUDY DESIGN: A prospective, consecutive cohort of 14 pregnant women requiring heparin therapy and 14 pregnant controls matched for age, race, and smoking status was identified by 20 weeks' gestation at a university medical center. Proximal femur bone density measurements were taken at baseline, immediately post partum, and 6 months post partum in the cases and controls. Vertebral measurements were also obtained on both groups immediately post partum and 6 months post partum. Bone density as a function of heparin dosing and duration was examined. Nonparametric statistical tests were used for all comparisons. RESULTS: Five of 14 cases (36%) had a > or = 10% decrease from the baseline proximal femur measurements to immediate postpartum values versus none of the 14 matched controls (p = 0.04). Mean proximal femur bone density measurements also decreased in the cases (p = 0.01); this difference continued to be statistically significant 6 months post partum (p = 0.03). No dose-response relationship could be demonstrated. CONCLUSION: Heparin adversely affected bone density in about one third of exposed patients.