Does breastmilk have brain benefits for preemies?

October 2, 2018

Babies born preterm are known to be at risk of alterations in brain structure and connectivity, but new research shows exposure to breastmilk may have cognitive benefits. PLUS: What’s behind postpartum opioid prescribing patterns? ALSO: How valuable is a second opinion for breast cancer diagnosis?

Babies born preterm are known to be at risk of alterations in brain structure and connectivity. Research by Scottish investigators shows that the structure of the white matter in their brains may improve with increased exposure to breastmilk.

Published in NeuroImage, the results are from a cohort of 47 infants born at ≤ 33 weeks treated at the Royal Infirmary in Edinburgh. They underwent brain magnetic resonance imaging at term-equivalent age as part of a longitudinal investigation of the effects of preterm birth on brain structure and outcome.

The researchers assessed the MRI results and information about the infants’ neonatal breastmilk exposure to test the hypothesis that breastfeeding is associated with improved markers of brain development and connectivity in preterm infants at term-equivalent age. Network-Based Statistics, Tract-based Spatial Statistics (TBSS), and volumetric analysis were used to investigate the effect of breastmilk exposure on white matter diffusion parameters, tissue volumes, and the structural connectome. 

Of the infants, 27 were exclusively breastfed for ≥ 75% of their time at the Royal Infirmary and 20 were breastfed for < 75% of that time. The higher exposure to breastmilk was associated with higher connectivity in the fractional anisotropy (FA)-weight connectome compared with the connectivity in the brains of the infants who had fewer breastmilk days (P= 0.04). 

Within the TBSS white matter skeleton, the infants who received more breastmilk had higher FA within the corpus callosum, cingulum cingulate gyri, centrum semiovale, corticospinal tracts, arcuate fasciculi and posterior limbs of the internal capsule. The difference between the two groups was unchanged after adjustment for postmenstrual age at birth or at image acquisition, bronchopulmonary dysplasia, and chorioamnionitis (P< 0.05). 

The investigators noted that the positive effects of breastmilk on the brain appeared to be dose-dependent, because connectivity in neural systems was further increased in infants who received breastmilk on ≥ 90% of days in the Royal Infirmary (P= 0.0086). The authors said the effects they observed are unlikely to be attributable to parenteral nutrition because exposure to it did not differ significantly between the two groups.

The main strength of the study, the researchers said, was the comprehensive assessment of brain development using three measures of the encephalopathy of prematurity: connectivity, tract microstructure, and local and global brain volumes. It was limited in that the authors could not investigate the effect of common genetic variation in metabolism of fatty acids and the cohort was not large enough to allow study of the effect of donor expressed breastmilk or human milk fortifier on brain development.

What’s behind postpartum opioid prescribing patterns?

Multiple factors have contributed to the current opioid epidemic, with physician over-prescribing known to play a major role. A new study in Obstetrics and Gynecology reveals characteristics of health care providers-and patients-that may be linked with postpartum opioid prescribing. 

The data are from a retrospective case-control study of all opioid-näive women who delivered at a large academic tertiary care center between December 1, 2015 and November 30, 2016. The authors accessed demographic and clinical information from outpatient and inpatient electronic medical records. Electronic medical and pharmacy records were used to determine the discharge health care provider, whether an opioid was prescribed at discharge, and if so, what type of opioid, what strength, and how many tablets.

The primary objective of the study was receipt of a high quantity of prescribed opioids at discharge, or morphine milligram equivalents (MME) ≥ 90thpercentile for the cohort, which was 300 MME for vaginal and 500 MME for cesarean delivery. The authors also included women patients who were not prescribed opioids at discharge for a comparison group. Women whose deliveries were vaginal were analyzed separately from those who had cesareans. 

Of the 12,320 women included in the analysis, 73.6% (n=9,038) underwent vaginal delivery and 26.6% (n=3,288) underwent cesarean delivery. The majority of women were non-Hispanic white (58.3%) and privately insured (52.5%). Approximately two-thirds (67.4%) of the participants were discharged by an attending physician, one-fourth (24.8%) were discharged by an advanced practitioner and 7.9% were discharged by a trainee physician. Female health care providers made up the majority (87.5%) of discharging physicians. 

Just under half (45.3%) of postpartum women received an opioid prescription on discharge. This included 30.3% (n=2,749) women who had a vaginal delivery and 86.7% (n=2,849) of women who had a cesarean delivery. Among women who had a vaginal delivery, 636 (7.0%) received high quantities of prescribed opioids at discharge and 241 (7.3%) of women who underwent cesarean delivery received a high amount at discharge. 

In terms of demographics, women who received high quantities of opioids were older and were more likely to be married, non-Hispanic white, and nulliparous. They were also more likely to have a history of depression and anxiety. Patient-specific factors associated with prescription of a high quantities of opioids included nulliparity, intrapartum neuraxial anesthesia, major laceration, and infectious complication. Patients who received the drugs at that level also were less likely to be discharged by a trainee physician (8.5% vs 1.9%; odds ratio [OR] 0.18, 95% CI 0.10-0.32). For women who underwent cesarean delivery, the only factor associated with high quantities of opioids was hemorrhage. 

The authors identified a few limitations to their study. The retrospective nature of the research made it susceptible to incomplete data and misclassification. The number of trainee physicians in the opioid prescription group was very low and the exact odds ratio may be imprecise. The data also lacked information regarding specific group differences in rounding practices or postpartum care. Finally, the study was limited to one academic institution. Despite these limitations, the authors believe that while patient factors account for some variation in postpartum prescribing habits for opioids at discharge, discharge by a trainee physician is independently associated with lower odds of high opioid prescribing. 

How valuable is a second opinion for breast cancer diagnosis?

Surgical second-opinion programs have continued to expand since their development in the 1970s but a standard for assessing whether the first or second opinion is correct does not exist. Results of a recent study suggests that for women with breast cancer, a second opinion about their diagnosis from a National Cancer Institute (NCI)-designated cancer center may change recommendations for imaging and referrals. 

Published in Annals of Surgical Oncology, the retrospective study reflected cases from August 2015 to March 2016 at the Medical University of South Carolina (MUSC). The researchers looked at data from patients who presented to MUSC for a second opinion after being diagnosed with breast cancer at an outside institution. Radiology, pathology and genetic testing reports from the other institutions were compared with the MUSC findings after review by a multidisciplinary tumor board (MTB) and subsequent testing. The authors then categorized the cases based on whether diagnostic variations were present or not. 

Charts from 70 patients were included in the analysis. After the MTB review, 43 (61%) of the 70 second opinions resulted in identification of additional calcifications or lesions, more imaging, or recommendations for additional breast or axillary biopsies. Furthermore, in 16 of the 43 women, additional ipsilateral, contralateral, or axillary lymph node metastases were found. Thirty additional biopsies also were done on 25 patients. Of them, 16 (64%) resulted in discovery of an additional cancer, which accounted for about 23% of the 70 patients presenting for a second opinion. 

Changes in pathology were not as dramatic and there were fewer as a result of the second opinions (14/70, 20%). The most frequent variation was a change in histology (10%). In regard to genetic testing, 11 of the 70 patients (15.7%) met National Comprehensive Cancer Network guidelines for testing but had not been offered it before their second opinions. Of those 11 women, two were found to have variants of unknown significance, but the finding did not change their disease management. 

Given the significant number of new or changed diagnoses acquired through additional testing and imaging in this study, the authors believe it illustrates the value of a second opinion from a MTB or women with breast cancer. However, they noted a few limitations of their research. 

They did not assess whether change in diagnosis resulted in change in management. The study also did not look at the clinical course of the individual tumors in relation to their pathologic diagnosis. As a result, it was not possible to determine whether the first or second diagnosis was more correct. The authors also pointed out that only six of the 70 patients seen had their first opinion at a medical research center.