BackgroundThe presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with increased mortality in several malignancies. Here, we quantify the effect of NLR on survival in patients with breast cancer, and examine the effect of clinicopathologic factors on its prognostic value.MethodsA systematic search of electronic databases was conducted to identify publications exploring the association of blood NLR (measured pre treatment) and overall survival (OS) and disease-free survival (DFS) among patients with breast cancer. Data from studies reporting a hazard ratio (HR) and 95% confidence interval (CI) or a P value were pooled in a meta-analysis. Pooled HRs were computed and weighted using generic inverse variance. Meta-regression was performed to evaluate the influence of clinicopathologic factors such as age, disease stage, tumor grade, nodal involvement, receptor status, and NLR cutoff on the HR for OS and DFS. All statistical tests were two-sided.ResultsFifteen studies comprising a total of 8563 patients were included. The studies used different cutoff values to classify high NLR (range 1.9–5.0). The median cutoff value for high NLR used in these studies was 3.0 amongst 13 studies reporting a HR for OS, and 2.5 in 10 studies reporting DFS outcomes. NLR greater than the cutoff value was associated with worse OS (HR 2.56, 95% CI = 1.96–3.35; P < 0.001) and DFS (HR 1.74, 95% CI = 1.47–2.07; P < 0.001). This association was similar in studies including only early-stage disease and those comprising patients with both early-stage and metastatic disease. Estrogen receptor (ER) and HER-2 appeared to modify the effect of NLR on DFS, because NLR had greater prognostic value for DFS in ER-negative and HER2-negative breast cancer. No subgroup showed an influence on the association between NLR and OS.ConclusionsHigh NLR is associated with an adverse OS and DFS in patients with breast cancer with a greater effect on disease-specific outcome in ER and HER2-negative disease. NLR is an easily accessible prognostic marker, and its addition to established risk prediction models warrants further investigation.

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BACKGROUNDCauses of early infant growth restriction remain incompletely understood. Where vitamin D deficiency is common, vitamin D supplementation during pregnancy and lactation may improve fetal-infant growth and other birth outcomes.METHODSWe conducted a randomized, double-blind, placebo-controlled trial of maternal vitamin D supplementation from 17-24 weeks gestation until birth or 6 months postpartum. Participants were randomly allocated to five vitamin D and/or placebo supplementation groups: (A) 0 IU/week, (B) 4200 IU/week, (C) 16800 IU/week, or (D) 28000 IU/week in pregnancy, all with 0 IU/week postpartum; or, (E) 28000 IU/week in prenatal and postpartum periods. The primary outcome was length-for-age z-score at one year of age according to World Health Organization child growth standards.RESULTSAmong 1164 infants assessed at one year of age (90% of 1300 pregnancies), there were no differences across groups in length-for-age z-scores (mean ±standard deviation): A: -0.93 ±1.05, B: -1.11 ±1.12, C: -0.97 ±0.97, D: -1.06 ±1.07, E: -0.94 ±1.00 (p=0.23). Groups were similar with respect to other anthropometric measures, birth outcomes, and morbidity. Vitamin D had dose- dependent effects on maternal and infant serum 25-hydroxyvitamin D and calcium, maternal urinary calcium excretion, and maternal parathyroid hormone concentrations. No clinical adverse events were attributed to the vitamin D intervention. CONCLUSIONSIn a population with widespread prenatal vitamin D deficiency and fetal/infant growth restriction, maternal vitamin D supplementation from mid-pregnancy until birth or 6 months postpartum does not influence fetal or infant growth, and has no beneficial or harmful effects on numerous other birth and infant outcomes.

CONTEXT: Periventricular/intraventricular hemorrhage (PIVH) is a common short-term morbidity in preterm infants, but its long-term neurodevelopmental impact, particularly with mild PIVH, remains unclear. STUDY SELECTION: Studies reporting long-term neurodevelopmental outcomes based on severity of PIVH were included.DATA EXTRACTION: Study characteristics, inclusion/exclusion criteria, exposures, and outcome assessment data extracted independently by 2 coauthors. RESULTS:The pooled unadjusted odds ratios of the primary outcome of death or moderate-severe neurodevelopmental impairment (NDI) were higher with both mild (1.48, 95% CI 1.26-1.73; 2 studies) and severe PIVH (4.72, 4.21-5.31; 3 studies); no studies reported adjusted odds ratios. Among survivors, odds of moderate-severe NDI were higher with mild and severe PIVH in both unadjusted (1.75, 1.40-2.20; 3 studies; 3.36, 3.06-3.68; 5 studies) and adjusted (1.39, 1.09-1.77; 3 studies; 2.44, 1.73-3.42; 2 studies) pooled analyses. Adjusted odds of cerebral palsy and cognitive delay were higher with severe but not mild PIVH.LIMITATIONS: Only observational studies were included. Fifteen of 21 included studies had a moderate-high risk of bias.CONCLUSIONS: Mild and severe PIVH are associated with progressively higher odds of death or moderatesevere NDI compared with no PIVH, but no studies adjusted for confounders. Among survivors, mild PIVH was associated with higher odds of moderate-severe NDI compared with no PIVH.

Maternal exposure to domestic violence was associated with significantly increased risk of low birth weight and preterm birth. Underreporting of domestic violence is hypothesized. Effective programs to identify violence and intervene during pregnancy are essential.

Increased stress, psychosocial problems, economic disadvantages, and lack of prenatal care are proposed to explain discrepancies in the outcome of unintended pregnancies. Studies of maternal intention and pregnancy outcomes have yielded varied results. Objective is to review studies of the risk of low birth weight (LBW)/preterm births (PTB) associated with unintended pregnancies ending in a live birth. We reviewed studies reporting on maternal intentions and outcomes from Medline, Embase, CINAHL, and bibliographies of identified articles. An unintended pregnancy was further classified as mistimed (not intended at that time) or unwanted (not desired at any time). Studies reporting an association between pregnancy intention and any of the outcomes were included. Study quality was assessed for biases in selection, exposure assessment, confounder adjustment, analyses, outcomes assessment, and attrition. Unadjusted and adjusted data from included studies were extracted by two reviewers. There were significantly increased odds of LBW among unintended pregnancies [odds ratio (OR) 1.36, 95% confidence interval (CI) 1.25, 1.48] ending in a live birth. Within the unintended category, mistimed (OR 1.31, 95% CI 1.13, 1.52) and unwanted (OR 1.51, 95% CI 1.29, 1.78) pregnancies were associated with LBW. There were statistically significantly increased odds of PTB among unintended (OR 1.31, 95% CI 1.09, 1.58), and unwanted (OR 1.50, 95% CI 1.41, 1.61) but not for mistimed (OR 1.36, 95% CI 0.96, 1.93) pregnancies. Unintended, unwanted, and mistimed pregnancies ending in a live birth are associated with a significantly increased risk of LBW and PTB.