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Pharmacotherapy for depression and bipolar disorder during lactation: A framework to aid decision making.
Sprague, J, Wisner, KL, Bogen, DL
Seminars in perinatology. 2020;(3):151224
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Abstract
OBJECTIVE Breastmilk is recommended as the exclusive source of nutrition for infants younger than 6 months due to the numerous health benefits for both infants and mothers. Although many women are prescribed medications during pregnancy and postpartum, limited data are available to assist women in weighing the benefits compared to the risks of peripartum medication use. The goals of this paper are to discuss the importance of breastmilk for the health of both the mother and infant, evaluate the impact of medication use on women's infant feeding choice, describe the transfer of drugs to breastmilk and infants, and provide a framework for clinicians to support evidence-based counseling for women treated for mood disorders. RECOMMENDATIONS We recommend early pregnancy counseling to discuss the benefits and risks of medications during breastfeeding. The Surgeon General's Call to Action (2011) highlights the short and long-term negative health effects of not providing breastmilk. Integrating recommendations from the pediatric and obstetric teams allows patients to make decisions based on evidence and reach their infant feeding goals. Databases containing summaries of research findings and pharmacologic properties of the drug of interest are an essential resource for clinicians.
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Anatomy and Physiology of the Breast during Pregnancy and Lactation.
Alex, A, Bhandary, E, McGuire, KP
Advances in experimental medicine and biology. 2020;:3-7
Abstract
The mature breast is located within the anterior thoracic wall, lying atop the pectoralis major muscle. Pubertal changes lead to incomplete development of the breast , a process which is only completed during pregnancy . The incomplete breast consists mostly of adipose tissue but also lactiferous units called lobes. These eventually drain into the lactiferous ducts and then into the lactiferous sinus and then to the nipple-areolar complex. During pregnancy , the breast undergoes both anatomic and physiologic changes to prepare for lactation. During the first trimester, the ductal system expands and branches out into the adipose tissue in response to the increase of estrogen. Elevated levels of estrogen also cause a decrease in adipose tissue and ductal proliferation and elongation. Estrogen also stimulates the pituitary gland which leads to elevated levels of prolactin. By the twentieth week of gestation, mammary glands are sufficiently developed to produce components of milk due to prolactin stimulation. Milk production is inhibited by high estrogen and progesterone levels and colostrum is produced during this time. In the third trimester and then rapidly after birth, these levels decrease, allowing for milk production and eventual let-down to allow for breastfeeding. Most pregnancies cause the areola to darken, the breast to increase in size, and the Montgomery glands to become more prominent. Post-lactational involution occurs at the cessation of milk production caused by a decline in prolactin.
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Cannabis Use During Lactation: Literature Review and Clinical Recommendations.
Ordean, A, Kim, G
Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC. 2020;(10):1248-1253
Abstract
Cannabis is the most commonly used psychoactive substance in Canada. The prevalence of cannabis use both during pregnancy and in the postpartum period has been estimated at 5% of the population. Women who use the drug during lactation place their infants at risk of exposure to cannabis and its metabolites in breast milk. This article provides a systematic review of infant outcomes associated with cannabis use by women during lactation followed by clinical recommendations. A review of the literature was conducted using Medline, Embase, and PsychInfo from their start to July 2018. Inclusion criteria consisted of articles addressing the impact of postpartum cannabis use by lactating women and providing developmental outcomes for infants. Two articles met these criteria and were included in our systematic review. Results indicate conflicting outcomes regarding the risk of exposure to cannabis in breast milk. Women should be advised to abstain from cannabis use during lactation or reduce consumption if abstinence is not possible. Furthermore, women should be advised to avoid breastfeeding within 1 hour of inhaled use to reduce exposure to highest concentration of cannabis in breast milk. Despite some evidence regarding health risks of post-natal exposure to cannabis, further research is needed to determine its impact on infant neurodevelopmental outcomes beyond the first year of life.
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The significant role of carnitine and fatty acids during pregnancy, lactation and perinatal period. Nutritional support in specific groups of pregnant women.
Manta-Vogli, PD, Schulpis, KH, Dotsikas, Y, Loukas, YL
Clinical nutrition (Edinburgh, Scotland). 2020;(8):2337-2346
Abstract
BACKGROUND & AIMS Pregnancy is characterized by a complexity of metabolic processes that may impact fetal health and development. Women's nutrition during pregnancy and lactation is considered important for both mother and infant. This review aims to investigate the significant role of fatty acids and carnitine during pregnancy and lactation in specific groups of pregnant and lactating women. METHODS The literature was reviewed using relevant data bases (e.g. Pubmed, Scopus, Science Direct) and relevant articles were selected to provide information and data for the text and associated Tables. RESULTS Dynamic features especially of plasma carnitine profile during pregnancy and lactation, indicate an extraordinarily active participation of carnitine in the intermediary metabolism both in pregnant woman and in neonate and may also have implications for health and disease later in life. Maternal diets rich in trans and saturated fatty acids can lead to impairments in the metabolism and development of the offspring, whereas the consumption of long chain-polyunsaturated fatty acids during pregnancy plays a beneficial physiologic and metabolic role in the health of offspring. CONCLUSIONS Pregnant women who are underweight, overweight or obese, with gestational diabetes mellitus or diabetes mellitus and those who choose vegan/vegetarian diets or are coming from socially disadvantaged areas, should be nutritionally supported to achieve a higher quality diet during pregnancy and/or lactation.
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Early-Life Effects of Vitamin D: A Focus on Pregnancy and Lactation.
Wagner, CL, Hollis, BW
Annals of nutrition & metabolism. 2020;:16-28
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Abstract
Vitamin D is an endocrine regulator of calcium and bone metabolism. Yet, its effects include other systems, such as innate and adaptive immunity. Unique to pregnancy, circulating 1,25-dihydroxyvitamin D (1,25[OH]2D) increases early on to concentrations that are 2-3 times prepregnant values. At no other time during the lifecycle is the conversion of 25-hydroxyvitamin D (25[OH]D) to 1,25(OH)2D directly related and optimized at ≥100 nmol/L. Vitamin D deficiency appears to affect pregnancy outcomes, yet randomized controlled trials of vitamin D supplementation achieve mixed results depending on when supplementation is initiated during pregnancy, the dose and dosing interval, and the degree of deficiency at the onset of pregnancy. Analysis of trials on an intention-to-treat basis as opposed to the use of 25(OH)D as the intermediary biomarker of vitamin D metabolism yields differing results, with treatment effects often noted only in the most deficient women. Immediately after delivery, maternal circulating 1,25(OH)2D concentrations return to prepregnancy baseline, at a time when a breastfeeding woman has increased demands of calcium, beyond what was needed during the last trimester of pregnancy, making one question why 1,25(OH)2D increases so significantly during pregnancy. Is it to serve as an immune modulator? The vitamin D content of mother's milk is directly related to maternal vitamin D status, and if a woman was deficient during pregnancy, her milk will be deficient unless she is taking higher doses of vitamin D. Because of this relative "deficiency," there is a recommendation that all breastfed infants receive 400 IU vitamin D3/day starting a few days after birth. The alternative - maternal supplementation with 6,400 IU vitamin D3/day, effective in safely raising maternal circulating vitamin D, that of her breast milk, and effective in achieving sufficiency in her recipient breastfeeding infant - remains a viable option. Additional research is needed to understand vitamin D's influence on pregnancy health and the effect of maternal supplementation on breast milk's immune signaling.
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Psychological Aspects of Pregnancy and Lactation in Patients with Breast Cancer.
Nejatisafa, AA, Faccio, F, Nalini, R
Advances in experimental medicine and biology. 2020;:199-207
Abstract
Young breast cancer patients face numerous challenges during the cancer trajectory. As in the last decade, women tend to delay pregnancies to a later time in life, and clinicians are often faced with young breast cancer patients who want to start a family or complete it. Becoming a mother is a delicate developmental process in which the woman redefines and restructures her identity as she gets prepared for her new role and responsibilities. When there is a history of cancer or cancer diagnosis is communicated during the pregnancy, fears, worries, and concerns emerge and specific support may be necessary. Follow-ups during the post-partum period are also recommended as lactation issues should not be overlooked. In this chapter, we analyze the psychological aspects of cancer survivors and women with pregnancy-associated breast cancer, and the management of these issues.
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Clinical lactation studies and the role of pharmacokinetic modeling and simulation in predicting drug exposures in breastfed infants.
Anderson, PO, Momper, JD
Journal of pharmacokinetics and pharmacodynamics. 2020;(4):295-304
Abstract
The relative lack of information on medication use during breastfeeding is an ongoing problem for health professionals and mothers alike. Most nursing mothers are prescribed some form of medication, yet some mothers either discontinue breastfeeding or avoid medications entirely. Although regulatory authorities have proposed a framework for clinical lactation studies, data on drug passage into breastmilk are often lacking. Model-based approaches can potentially be used to estimate the passage of drugs into milk, predict exposures in breastfed infants, and identify drugs that need clinical lactation studies. When a human study is called for, measurement of the drug concentration in milk are often adequate to characterize safety. Data from these studies can be leveraged to further refine pharmacokinetic models with subsequent Monte Carlo simulations to estimate the spread of exposure values. Both clinical lactation studies and model-based approaches have some limitations and pitfalls which are discussed.
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8.
Human milk fatty acid profile across lactational stages after term and preterm delivery: A pooled data analysis.
Floris, LM, Stahl, B, Abrahamse-Berkeveld, M, Teller, IC
Prostaglandins, leukotrienes, and essential fatty acids. 2020;:102023
Abstract
BACKGROUND Lipids in human milk (HM) provide the majority of energy for developing infants, as well as crucial essential fatty acids (FA). The FA composition of HM is highly variable and influenced by multiple factors. We sought to increase understanding of the variation in HMFA profiles and their development over the course of lactation, and after term and preterm delivery, using a pooled data analysis. OBJECTIVE To review the literature and perform a pooled data analysis to qualitatively describe an extensive FA profile (36 FAs) in term and preterm colostrum, transitional - and mature milk up to 60 days postpartum. DESIGN A Medline search was conducted for HMFA profile data following term or preterm delivery. The search was confined to English language papers published between January 1980 and August 2018. Studies reporting original data, extensive FA profiles in HM from healthy mothers were included. Weighted least squares (WLS) means were calculated from the pooled data using random or fixed effect models. RESULTS Our pooled data analysis included data from 55 studies worldwide, for a total of 4374 term milk samples and 1017 preterm milk samples, providing WLS means for 36 FAs. Patterns in both term and preterm milk were apparent throughout lactation for some FAs: The most abundant FAs (palmitic, linoleic and oleic acid) remained stable over time, whereas several long-chain polyunsaturated FAs (including ARA and DHA) seemed to decrease and short- and medium-chain FAs increased over time. CONCLUSIONS High heterogeneity between individual studies was observed for the reported levels of some FAs, whereas other FAs were remarkably consistent between studies. Our pooled data suggests that specific FA categories fluctuate according to distinct patterns over the course of lactation; many of these patterns are comparable between term and preterm milk.
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Physical Breast Examination in Pregnancy and Lactation.
Alipour, S
Advances in experimental medicine and biology. 2020;:9-16
Abstract
Physical exam of the breast is a very important part of breast assessment both for breast cancer screening, and when approaching breast lesions. Examination during pregnancy and breastfeeding follows exactly the same method as non-pregnancy periods. However, physical changes that occur in the breast during these times due to hormonal effects cause alterations that can on one hand conceal some pathologic disorders, and may on the other hand appear as pathologic findings while being purely physiologic. This chapter focuses first on some key points for an accurate breast examination, and then reviews some challenging controversial findings that may be noticed during breast exam in a pregnant or lactating woman.
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The Implausibility of Neonatal Opioid Toxicity from Breastfeeding.
Zipursky, J, Juurlink, DN
Clinical pharmacology and therapeutics. 2020;(5):964-970
Abstract
The belief that newborns can develop opioid toxicity from breastfeeding is widely held but supported by very little data. Based largely on a single, highly publicized case report (the "Toronto case"), major health agencies worldwide now caution against codeine use by nursing mothers. As a result, "stronger" opioids with greater abuse liability are increasingly prescribed in its place, potentially to the detriment of maternal health. We re-examine aspects of this case report to demonstrate why such an occurrence is highly implausible. The Toronto case involved the death of a 13-day-old infant from opioid toxicity. The child's mother, who took codeine while breastfeeding, was found to have a duplication of CYP2D6*2, consistent with ultrarapid metabolizer status. This led to the conclusion that the child died from opioid toxicity due to enhanced maternal conversion of codeine to morphine, with the subsequent passage of large amounts of morphine into breast milk. We argue that this explanation is implausible based upon several factors: (1) the exceedingly small amount of opioids passed into breastmilk irrespective of maternal CYP genotype, (2) the observation that significant neonatal opioid accumulation can only occur in the setting of severely impaired renal function, and (3) the previously unreported finding of a markedly elevated codeine concentration in postmortem blood. Finally, a review of the literature identifies a paucity of convincing reports of neonatal opioid toxicity during breastfeeding, with no other confirmed cases of neonatal death despite the use of these drugs by millions of nursing mothers over the past 2 decades.