2020 Cochrane Review Update: NSAIDs vs Other Analgesics for Soft Tissue Injury
BACKGROUND AND PURPOSE:
The best drug treatment for acute soft tissue injuries (bruise, sprains, strains, etc.) is not well known
NSAIDs are commonly recommended
Oral opioids for acute pain management may be leading to dependence
In an update to a 2015 Cochrane review, Jones et al. (Cochrane Database Syst. Rev. 2020) assessed the benefits or harms of NSAIDs compared with other oral analgesics for treating acute soft tissue injuries
METHODS:
Systematic review and meta-analysis
Data sources
CENTRAL | MEDLINE | Embase to January 2020
Other databases were searched to February 2019
Inclusion criteria
Randomized or quasi-randomized controlled trials
Trials included individuals soft tissue injury
Compared oral NSAIDs vs
Paracetamol (acetaminophen)
Opioid
Paracetamol plus opioid
Complementary and alternative medicine
Study design
Acute soft tissue injury definition: Sprain, strain, or contusion of a joint, ligament, tendon, or muscle occurring within 48 hours of inclusion in the study
Two review authors independently assessed studies for eligibility, extracted data, and assessed risk of bias
Quality of the evidence was assessed using GRADE criteria
Primary outcomes
Pain
Swelling
Function
Adverse effects
Early re-injury
RESULTS:
20 studies included | Combined total of 3305 participants
3 studies included children only | Remainder included predominantly young adults
Approximately 60% were male | 40% female
7 studies recruited only people with ankle sprains
Certainty
Evidence related to pain relief was generally high certainty
There was a combination of certainty with most outcomes
No studies reported re-injury rates
No studies compared NSAIDs with oral complementary and alternative medicines
RCT Results: Does Remdesivir Improve Clinical Status in Patients with Moderate COVID-19?
BACKGROUND AND PURPOSE:
In a controlled trial, remdesivir provided a clinical benefit to patients with severe COVID-19
Spinner et al. (JAMA, 2020) assessed the efficacy of 5 or 10 days of remdesivir treatment compared with standard care in patients with moderate COVID-19
METHODS:
Randomized, open-label trial (enrollment from March 15 to April 18, 2020)
Setting
105 hospitals in the United States, Europe, and Asia
Participants
Hospitalized
Confirmed COVID-19
Moderate disease: Pulmonary infiltrates and room-air oxygen saturation >94%
Interventions
10-day course of remdesivir
5-day course of remdesivir
Standard care
Study design
1:1:1 randomization
Remdesivir dosing: 200 mg IV on day 1 followed by 100 mg/d
Clinical status: 7-point ordinal scale ranging from death (category 1) to discharged (category 7)
Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios (OR)
An OR greater than 1 indicated difference in clinical status distribution in favor of category 7
Primary outcome
Clinical status on day 11
RESULTS:
583 patients began the study | 91% completion
Median age: 57 (IQR 46 to 66) years | 39% women
Comorbidities
Cardiovascular disease: 56%
Hypertension: 42%
Diabetes: 40%
Intervention groups
10-day remdesivir: 197 patients
5-day remdesivir: 199 patients
Standard care: 200 patients
Median length of treatment
5-day group: 5 days
10-day group: 6 days
Patients in the 5-day remdesivir group had significantly higher odds of a better clinical status (day 11) than those receiving standard care (P=0.02)
OR 1.65 (95% CI, 1.09 to 2.48)
No significant difference was seen in clinical status distribution on day 11 between the 10-day remdesivir group and the standard care group (P = 0.18)
Mortality by day 28
5-day remdesivir: 1% (2 patients)
10-day remdesivir: 2% (3 patients)
Standard care: 2% (4 patients)
Side effects were more common in the remdesivir treated patients vs standard care group for the following
Nausea (10% vs 3%)
Hypokalemia (6% vs 2%)
Headache (5% vs 3%)
CONCLUSION:
For patients with moderate COVID-19, a 10-day course of remdesivir had no significant impact on clinical status at day 11, compared to standard care
However, for a shorter course, authors conclude that
Is Pregnancy After Breast Cancer Safe for Women with BRCA Mutations?
BACKGROUND AND PURPOSE:
Pregnancy after breast cancer appears to be safe and is not associated with an increased risk of cancer recurrence
However, data are limited regarding pathogenic BRCA variants
Lambertini et al. (Journal of Clinical Oncology, 2020) investigated the impact of pregnancy on breast cancer outcomes in patients with germline BRCA mutations
METHODS:
Multicenter, retrospective cohort study (January 2000 and December 2012
Participants
Breast cancer diagnosis ≤ 40 years
Deleterious germline BRCA mutations
Exposures
Pregnancy after breast cancer
No pregnancy
Study design
Survival analyses | Adjusted for known prognostic factors including adjusted for age at diagnosis, tumor size, nodal status, hormone receptor status, type of endocrine therapy, breast surgery, and BRCA mutation
Primary outcomes
Pregnancy rate
Disease-free survival (DFS)
Secondary outcomes
Pregnancy outcomes
Overall survival (OS)
RESULTS:
1252 patients were included
BRCA1: 811 patients
BRCA2: 430 patients
BRCA1/2: 11 patients
Median age at time of pregnancy: 35.7 years | Median time from diagnosis to pregnancy 4.5 years
195 women had at least 1 pregnancy after breast cancer
Pregnancy outcomes
Pregnancy rate at 10 years: 19% (95% CI, 17% to 22%)
Induced abortions: 8.2%
Miscarriages: 10.3%
Births: 76.9% of women | 9.2% preterm
Adverse outcomes
Pregnancy complications: 11.6%
Congenital anomalies: 1.8%
Median follow-up from breast cancer diagnosis was 8.3 years
No differences in survival detected between the pregnancy and nonpregnancy groups
Disease free survival
Adjusted hazard ratio (HR) 0.87 (95% CI, 0.61 to 1.23)
P = 0.41
Overall survival
Adjusted HR 0.88 (95% CI, 0.50 to 1.56)
P = 0.66
CONCLUSION:
Pregnancy after breast cancer in patients with BRCA mutations is not associated with unfavorable survival outcomes or pregnancy outcomes
For women with BRCA mutations, pregnancy after breast cancer is safe and does not worsen prognosis
MifeMiso RCT results: Mifepristone Plus Misoprostol or Misoprostol Alone for Miscarriage Treatment?
BACKGROUND AND PURPOSE:
Chu et al. (The Lancet, 2020) examined whether treatment with mifepristone plus misoprostol resulted in a higher rate of completion of missed miscarriage vs misoprostol alone
Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso) Trial
Participants
≥16 years
Missed miscarriage | Diagnosed by pelvic ultrasound up to 14 weeks GA
Patient opts for medical management of miscarriage
Interventions
Mifepristone group
Single 200 mg dose of oral mifepristone
Followed by a single dose of vaginal, oral, or sublingual misoprostol 800 μg 2 days later
Control group
Oral placebo
Followed by a single dose of vaginal, oral, or sublingual misoprostol 800 μg 2 days later
Study design
1:1 randomization | Study group balancing performed for the following
Maternal age (<30 years vs ≥30 years)
Body-mass index (<35 kg/m2 vs ≥35 kg/m2)
Previous parity (nulliparous women vs parous women)
Gestational age (<70 days vs ≥70 days)
Amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3)
Randomizing center
Masking: Participants, clinicians, pharmacists, trial nurses, and midwives masked to study group assignment throughout the trial
Power analysis: 335 women in each trial group required to provide 90% power to detect a difference of ten percentage points for primary outcome
Analyses based on intention-to-treat
Primary outcome
Failure to spontaneously pass the gestational sac within 7 days after assignment
RESULTS:
711 women were randomized
Mifepristone and misoprostol group (mifepristone): 357 women
Placebo and misoprostol group (control): 354 women
Fewer women in the mifespristone group did not pass the gestational sac spontaneously within 7 days
Mifepristone: 17%
Control: 24%
Risk ratio (RR) 0.73 (95% CI, 0.54 to 0.99; p=0.043)
Fewer women in the mifepristone group required surgical intervention to complete the miscarriage
Mifepristone: 17%
Control: 25%
RR 0.71 (95% CI, 0.53 to 0.95; p = 0.021)
No subgroup effect was noted based on GA
Adverse events: There was no difference between groups
CONCLUSION:
The combination of mifepristone and misoprostol was more effective for the treatment of missed miscarriage than misoprostol alone
Benefits include reduced need for surgical intervention
The authors recommend
…women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery
Cochrane Review: Oral or Intra-Vaginal Anti-Fungal Treatment for Candidiasis?
BACKGROUND AND PURPOSE:
This Cochrane review by Denison et al. (Cochrane Database Sys Rev, 2020) is the second update of the original review
The authors assessed the effectiveness of oral versus intravaginal antifungals for the treatment of uncomplicated vulvovaginal candidiasis
METHODS:
Systematic review and meta-analysis
Inclusion criteria
RCTs
Any language
Trials that compared at least one oral antifungal with one intravaginal antifungal
Participants: Women ≥ 16 years | Positive mycological diagnosis of uncomplicated vulvovaginal candidiasis
Exclusion: HIV positive | Imunocompromised | Pregnant | Breast feeding | Diabetic
Primary outcome
Relative effectiveness of clinical cure (presence of symptoms)
Secondary outcomes
Relative effectiveness for mycological cure
Safety | Side effects | Treatment preference | Time to first relief of symptoms | Costs
RESULTS:
26 trials | 5007 participants
Trials were conducted in multiple countries
Overall risk of bias deemed to be high
8 different medications were included (imidazole and triazole)
Oral vs Intravaginal Antifungals for Clinical Cure
There was probably little or no difference between oral and intravaginal anti-fungal treatment for clinical cure
Short-term follow-up (5 to 15 days)
Odds ratio (OR) 1.14 (95% CI, 0.91 to 1.43; 13 trials; 1859 participants)
Moderate-certainty evidence
Long-term follow-up (2 to 12 weeks)
OR 1.07 (95% CI, 0.77 to 1.50; 9 trials; 1042 participants)
Moderate-certainty evidence
Oral treatment probably improves mycological cure over intravaginal treatment at
Short-term follow-up
OR 1.24 (95% CI, 1.03 to 1.50: 19 trials; 3057 participants)
Moderate-certainty evidence
Long-term follow-up
OR 1.29 (95% CI, 1.05 to 1.60; 13 trials; 1661 participants)
Moderate-certainty evidence
Oral vs IntraVaginal Antifungals for Safety and Satisfaction
Safety
Low risk of participants withdrawing from the studies due to adverse drug effects for either treatment
23 trials; 4637 participants
High-certainty evidence
It is undetermined whether oral treatments reduced the number of side effects compared with intravaginal treatments
OR 1.04 (95% CI, 0.84 to 1.29; 16 trials; 3155 participants)
Low-certainty evidence
The type of side effects differed
Intravaginal: Local reactions
Oral: Systemic effects | Especially GI symptoms and headaches
Patient satisfaction
Oral treatment was favored by participants
12 trials; 2206 participants
Low-certainty evidence
Little or no difference in time to first relief of symptoms was seen between oral vs intravaginal treatments
10 trials; 1910 participants
Low-certainty evidence
Costs were not reported in any trial
CONCLUSION:
Compared to intra-vaginal anti-fungal treatment, oral treatment does not appear to make a difference when it comes to clinical cure (perceived symptoms) but probably does improve clearance of candida from vaginal canal when compared to vaginal treatment
Oral treatment was also preferred by participants, though certainty of evidence was low
Upon review of these the results, Cochrane Reviews states that
The addition of new evidence does not change the conclusions of the review. The results of this review should be considered stable in terms of the antifungal medicines included. The frequency of future updates should be limited. No further updates are planned
Lynch syndrome, formerly known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is the most common hereditary cause of colon and endometrial cancer, and is thought to explain 3-5% of colorectal cancer cases. Approximately 1 in 279 American are affected with Lynch syndrome.
What causes Lynch Syndrome?
Lynch syndrome is caused by genetic changes, also called mutations, in one of 5 genes (a segment of DNA that codes for protein)
Most of these genes are involved in DNA repair – and act as the ‘spellcheckers’ of the cell
If there is a “spelling error” (a new change in the DNA code), these genes fix the error before the DNA copies itself to make more new cells
Because of the work they do, they are called mismatch repair (MMR) genes
People that have Lynch syndrome are missing a working copy of one of these five genes and therefore accumulate genetic damage faster than average
Cancer is caused by an accumulation of genetic errors within cells
When a person has an inherited mutation in an MMR gene, the DNA repair process no longer works as efficiently as it should
Without these working repair genes, the damage builds up and these individuals are more likely to develop certain types of cancer
Individuals with Lynch syndrome are at increased risk for developing specific cancers such as
According to the National Comprehensive Cancer Network (NCCN), the most significant cancer risks are for
Colorectal cancer: 12 to 52% lifetime risk (compared to 5% for people with average risk)
Uterine (endometrial) cancer: up to 57% lifetime risk (compared to 3% for people with average risk)
How do Doctors Figure out if Someone has Lynch Syndrome?
There Are a Few Ways That a Person May Be Diagnosed with Lynch Syndrome
Testing cancer cells of someone who has colon cancer or endometrial cancer
Testing can be done on a piece of the tumor that can identify signs of poor DNA repair or missing repair proteins
Genetic testing to look for changes in the 5 Lynch syndrome repair genes
Done on a blood or saliva sample if there is a personal or family history suggestive of Lynch syndrome
Who Might Be Offered Genetic Testing For Lynch Syndrome?
The following questions can be used to help identify people who may be at higher risk
Has there been anyone affected with colorectal or uterine cancer before the age of 50?
More than one cancer, of any kind, in the same person (such as colon and uterine cancer)?
10 or more colorectal polyps during someone’s lifetime?
Three or more family members (on the same side of the family) with colon, uterine or stomach cancer?
Numerous family members with colon cancer or other cancers?
Note: If you or someone in your family answers ‘yes’ to any of the above questions, a genetic counselor can help you decide if genetic testing for Lynch syndrome is a good idea
How is Lynch Syndrome Passed Along in Families?
Lynch Syndrome Is A Dominantly Inherited Condition
This means that a mutation in one copy of a MMR gene is sufficient to cause an increased risk for cancer
Individuals who inherit Lynch syndrome have a 50% chance to pass it onto each of their children
Testing children for Lynch syndrome usually occurs after the age of 18 because individuals with Lynch syndrome are not at an increased risk for childhood cancers
Individuals who did not inherit an MMR mutation do not have Lynch syndrome and therefore cannot pass it onto their children
Note: Since Lynch syndrome is an inherited condition, it is important to let family members know they may be at risk too | To protect your privacy, nobody should ever reach out to your family members without your knowledge and permission
How Does Knowing if You Have Lynch Syndrome Help if You Don’t Have Cancer?
Identifying people with Lynch syndrome is the best way to start early detection and prevent cancer
Colon Cancer Prevention
To reduce the risk of cancer, a person with Lynch syndrome will be offered extra screening, for example
Starting colonoscopy: Individuals with Lynch syndrome will begin colonoscopies at age 20 to 25 or 2 to 5 years before the earliest colorectal cancer in their family, compared to the general population start date at age 50
Timing of colonoscopy: Individuals with Lynch syndrome will get colonoscopies done every 1 to 2 years compared to the general population interval which is every 10 years
Note: A genetic counselor or oncologist will explain the details of an appropriate screening program for someone who is affected with Lynch syndrome | A colonoscopy is the only screen that can prevent colon cancer!
Uterine and Ovarian Cancer Prevention
There are recommended risk reduction options
Surgery: The National Comprehensive Cancer Network (NCCN) recommends a hysterectomy (removing the uterus) and oophorectomy (removing the ovaries) in women between the ages of 35-40 or after childbearing is complete
Medicine: Studies show that aspirin therapy in people who have Lynch syndrome lowers their risk of colon cancer and other cancers
Preimplantation Genetic Testing (PGT)
Since there is a 50% chance that a child will inherit a non-working MMR gene from a parent, some couples, where one of the prospective parents has Lynch syndrome, may consider PGT when it comes time to have a child
PGT is used together with invitro fertilization (IVF)
Fertilization occurs outside of the uterus
The embryo is tested and only embryos with normal functioning MMR genes are transferred to uterus
PGT can
Prevent genetic conditions, such as Lynch syndrome, from being passed onto a child
Eliminate a familial inherited genetic syndrome in future generations
KNOW YOUR RIGHTS
Genetic Information Non-discrimination Act of 2008 (GINA)
GINA prohibits the use of an individual’s genetic information to affect their eligibility or premium regarding health insurance and Medicare supplemental policies
GINA prohibits employers from requesting genetic information about their employees
GINA only protects predictive genetic information (such as increased susceptibility to cancer)
It will not protect an individual if they have manifested disease
GINA does not apply to
Life insurance
Disability insurance
Long-term care insurance
Who is not covered by GINA?
Members and families in the United States Military
Veterans who receive care through the Veteran’s Administration (VA)
Native American health service members
Federal employees covered by the Federal Employee Benefits Program (FEHB)
People who work for groups with 15 employees or less
The DNA@ObG entries are meant for healthcare providers to share with patients as an educational tool. They are not intended as and do not constitute or substitute for medical or healthcare advice or diagnosis, and may not and should not be used for such purposes. Individuals should always consult with a qualified healthcare provider about their specific circumstances, including before starting or stopping any treatment, medical or otherwise. DNA@ObG content via this web site is provided with the understanding that The ObG Project is not engaged in rendering medical, counseling, legal, or other professional services or advice.
Hereditary Breast and Ovarian Cancer (HBOC) Syndrome
Hereditary Cancer: What is it?
Hereditary cancer is due to an inherited change in a gene (genetic mutation) that can be passed down through the generations
Only 5-10% of cancers are hereditary
Every person inherits numerous genes that protect them against cancer
Hereditary cancer is associated with an increased risk for cancer because one of these cancer protection genes does not work properly
People who have a mutation in a cancer susceptibility gene are born with these changes and can pass them on to their children
A genetic test can ’read’ the DNA code of specific genes and determine
If the DNA code is correct, which means the genes are working properly, or
If there is a serious genetic change that may interfere with how the gene works and therefore lead to an increased risk for cancer
These changes mean that a person is more at risk or ‘susceptible’ to certain cancers, but not all individuals with these genetic mutations will develop cancer
Learning that you have an inherited change in a gene that causes increased cancer susceptibility can help you learn more about your cancer risks and help you manage your health accordingly
A person with a higher chance of developing cancer may need modified screening recommendations that are tailored to their genetic risk
For example, mammograms may start when a woman is 25 instead of 40, and may occur more frequently
Hereditary Breast, Ovarian, and Pancreatic Cancer: Basics
People with this syndrome are at risk for developing certain types of cancer such as
Breast, ovarian, pancreatic, male breast cancer, prostate cancer, melanoma and others
Approximately 1 in 400 to 1 in 800 Americans have HBOC
Mutations or changes in the genes BRCA1 and BRCA2 are the most common cause of HBOC
BRCA1 and BRCA2 are tumor suppressor genes that are designed to protect us against cancer
When a person inherits a non-working copy of one of these genes, caused by a genetic mutation, they have an increased chance of developing cancer
Breast cancer
Mutations in BRCA1 and BRCA2 account for 50% of hereditary breast cancers
Ovarian cancer
Inherited genetic mutations are involved in more than 20% of ovarian cancers
Of that 20%, 65-85% of those mutations are in the BRCA1 and BRCA2 genes
Pancreatic Cancer
Pancreatic cancer has now been added to what is commonly known as Hereditary Breast and Ovarian Cancer Syndrome
Note: While people are most familiar with BRCA1 and BRCA2 genes, there are other genes that are associated with this syndrome (examples include PALB2, CHEK2, and TP53, among others)
How Much Higher is the Risk for Cancer with HBOC?
BRCA1
Female Breast Cancer
To age 50: 28% to 51% vs 1.9% in general population
To age 70: 46% to 87% vs 7.1% in the general population
Ovarian Cancer
To age 50: 8% To 23% vs 0.2% in the general population
To age 70: 39% to 63% vs 0.7% in the general population
Pancreatic Cancer
To age 80: Elevated risk vs 1% in the general population
BRCA2
Female Breast Cancer
To age 50: 23% to 35% vs 1.9% in general population
To age 70: 43% to 84% vs 7.1% in the general population
Ovarian Cancer
To age 50: 0.4% To 4% vs 0.2% in the general population
To age 70: 15% to 27% vs 0.7% in the general population
Pancreatic Cancer
To age 80: up to 7% vs 1% in the general population
Are you at risk for HBOC?
You may be at risk if you answer yes to any of the following questions
Have you or anyone in your family been diagnosed with breast cancer at or before the age of 45, or triple-negative breast cancer at or before the age of 60?
Have you or anyone in your family been diagnosed with more than one cancer?
Such as two breast cancers, or breast and ovarian cancer
Have you or anyone in your family been diagnosed with a rare cancer?
Such as ovarian cancer or male breast cancer
Do you have multiple family members on one side of the family that have had breast, ovarian or other cancers?
Do you have Ashkenazi Jewish ancestry?
Has anyone in your family been found to carry a genetic mutation that increases their risk for cancer?
Note: If you answered yes to any of these questions, you may want to talk to your doctor about genetic testing or seeing a genetic counselor
Cancer Genetic Testing
A genetic test can help determine if the DNA sequence in your cancer protection genes is correct, or if there is a genetic change that may cause the genes to malfunction and therefore increase your susceptibility to cancer
Traditionally a genetic test just looked at the two genes, BRCA1 and BRCA2
It is becoming more common to look at many more genes at once
Genetic panels can range from a few to more than 80 genes associated with different types of cancer and cancer predisposition syndromes
By discussing your situation with a genetic counselor and your physician, you can determine which is the right test for you
How Can A Genetic Test Impact Your Health Or Your Family’s Well-Being?
If you are found to have a cancer predisposition syndrome such as HBOC, your doctor can help personalize your cancer screening and discuss preventative medical and surgical options with you, such as
Breast cancer screening, including breast MRIs and mammograms, can start at an earlier age and be done more often
However, monitoring with mammograms and MRI is not a preventative strategy but rather an approach that can be used for early detection
Medications and surgeries that can reduce your chance of developing breast or ovarian cancer
A care plan to look for changes that may give rise to related cancers
The goal is usually to find problems early, often before they actually become malignant and can be treated with simpler procedures rather than with chemotherapies or major surgeries
For example, yearly skin examinations to look for suspicious-looking moles that may become melanomas, or colonoscopies to look for polyps before they become colorectal cancers
Genetic results may be difficult to understand and are rarely clear-cut:
A genetic counselor can help you understand your results and clarify any inherited risks to you or your family (see related DNA@ObG entry on Cancer Basics)
The goal is always to help you make decisions that are right for you
Inheritance
Who is at risk?
If you are found to carry a genetic mutation in a gene that increases your risk for cancer, your first-degree family members (brothers/sisters, parents, and children) have a 50% chance of having the same mutation that you have
It is important to remember that even through the name, Hereditary Breast and Ovarian Cancer Syndrome, sounds like it only affects women, both men and women have the same chance of inheriting a mutation that causes HBOC
Recently, professional societies have included pancreatic cancer along with breast and ovarian cancer as part of the HBOC syndrome
Men are also at risk for prostate cancer, pancreatic cancer, male breast cancer and melanoma
KNOW YOUR RIGHTS
Genetic Information Non-discrimination Act of 2008 (GINA)
GINA prohibits the use of an individual’s genetic information to affect their eligibility or premium regarding health insurance and Medicare supplemental policies
GINA prohibits employers from requesting genetic information about their employees
GINA only protects predictive genetic information (such as increased susceptibility to cancer)
It will not protect an individual if they have manifested disease
GINA does not apply to
Life insurance
Disability insurance
Long-term care insurance
Who is not covered by GINA?
Members and families in the United States Military
Veterans who receive care through the Veteran’s Administration (VA)
Native American health service members
Federal employees covered by the Federal Employee Benefits Program (FEHB)
People who work for groups with 15 employees or less
The DNA@ObG entries are meant for healthcare providers to share with patients as an educational tool. They are not intended as and do not constitute or substitute for medical or healthcare advice or diagnosis, and may not and should not be used for such purposes. Individuals should always consult with a qualified healthcare provider about their specific circumstances, including before starting or stopping any treatment, medical or otherwise. DNA@ObG content via this web site is provided with the understanding that The ObG Project is not engaged in rendering medical, counseling, legal, or other professional services or advice.
Drugs & Radiation: Drugs in Pregnancy and Breastfeeding – Helpful Resources
SUMMARY:
Many women who are newly pregnant or planning on getting pregnant will be confronted by decisions regarding their medications. While most medications during pregnancy are safe for the baby, it is important to note that some medications can cause birth defects, developmental disabilities, prematurity, or miscarriage. Identifying which medications are safe and how to best support you before pregnancy, during the pregnancy, and after birth, is an important conversation that should happen with your doctor.
Staying Healthy During Pregnancy
Medication during pregnancy is extremely common
Most women take at least one medication during their pregnancy
Many women have chronic conditions that require medication during pregnancy including
High blood pressure | Asthma | Diabetes | Depression
Pregnancy can induce new health problems or make old health problems that need treatment recur
As a woman’s body and weight shift during pregnancy, the amount of medication she takes (dosage) may need to change as well
While it is important not to start any new medications in pregnancy without speaking to your obstetric provider, it is just as important not to stop or change how you take your medications without a discussion
A basic principle is that a healthy mother gives a baby the best chance of a good outcome
Some women need to take medicines throughout their pregnancy to help control certain health conditions | Stopping some of these medications could be detrimental to mother and baby
Common examples: Stopping drugs that prevent seizures or asthma attacks may result in a relapse and could harm the pregnancy
Dose and timing: Some medicines are safe during certain parts of the pregnancy and unsafe during others | Modifying how much medicine you take could create a safer option for mother and baby
Some medications are known to cause birth defects and should be avoided (e.g. oral isotretinoin also known as Accutane®)
However, many medications are safe or have not been found to be associated in humans with birth defects or harm to the baby
When discussing medications with your provider, make sure to include all drugs or substances you use or have taken recently, including vitamins, or herbal or ‘natural’ supplements, as they may have important biologic effects
What if You Take Medications Before You Know You’re Pregnant?
Many women will take certain substances before they know they are pregnant
While some of these exposures may be concerning, most are not likely to cause harm. A discussion with a healthcare provider or a referral to genetic specialists, when necessary, will usually sort out if there are any issues
Factors taken into consideration when determining if a drug is dangerous in pregnancy include the following
How much medication is taken (the dose)
When during the pregnancy the medication is taken
Other health conditions a woman might have
Other medications a woman is taking
Breastfeeding and Medication
There is much evidence that shows the clear benefits of breastfeeding, and many medications are considered safe to use while breastfeeding | CDC provides excellent information on the benefits of breastfeeding (see ‘Learn More – Primary Sources’ below)
However, some medications may pass into breast milk and be of concern
This is important information to know because some new mothers may have medical conditions that will require treatment after delivery
What if You Need to Take Medication While Nursing?
Women who are nursing should have open conversations with their physician and pharmacist about any medications that they may be taking or want to take
Healthcare professionals are well aware of the many benefits of breastfeeding and will work with a mother to prevent medication from being a roadblock to breastfeeding whenever possible
Hot topic: Breastfeeding and COVID-19
In general, breast milk is ideal for infants, including newborns whose mothers have COVID-19
There may be some concerns where women with COVID-19 are on experimental medication | Your physician will discuss risks and benefits of these drugs including breast feeding
There are some researchers (such as MotherToBaby – see references below) that are studying pregnancy, breastfeeding and COVID-19 and are actively enrolling new mothers with confirmed or suspected COVID-19 infection into their studies
Where to find information about drugs in pregnancy
The CDC strongly cautions against making decisions based on ‘lists you find online’ and goes on to state
Instead use the lists as a starting point to talk with your doctor. Don’t stop or start taking any type of medication that you need without first talking with a healthcare provider. A conversation with a healthcare provider can help ensure that you are taking only what is necessary.
From ‘About Us’: MotherToBaby, a service of the non-profit Organization of Teratology Information Specialists (OTIS), is the nation’s leading authority and most trusted source of evidence-based information on the safety of medications and other exposures during pregnancy and while breastfeeding. Our information service is available to mothers, healthcare professionals, and the general public. They are also conducting studies related to COVID-19 and breastfeeding
The DNA@ObG entries are meant for healthcare providers to share with patients as an educational tool. They are not intended as and do not constitute or substitute for medical or healthcare advice or diagnosis, and may not and should not be used for such purposes. Individuals should always consult with a qualified healthcare provider about their specific circumstances, including before starting or stopping any treatment, medical or otherwise. DNA@ObG content via this web site is provided with the understanding that The ObG Project is not engaged in rendering medical, counseling, legal, or other professional services or advice.
Universal Screening on Admission to Labor Floor: Latest COVID-19 Prevalence Results
PURPOSE:
Many hospitals have implemented universal COVID-19 screening for all women admitted for delivery
An NYC health system found a 13.5% prevalence of infection in asymptomatic women early in the pandemic
Miller et al. (Obstetrics & Gynecology, 2020) examined the prevalence rates of infection with universal screening in Chicago
METHODS:
Prospective case series
Setting
Chicago hospital system (April 8 to April 27, 2020)
Acceleration phase of the pandemic
Participants
Pregnant women
Admitted to the hospital for delivery
Study design
Universal COVID-19 testing for delivery: Implemented April 8
Scheduled deliveries: Tested 12 to 36 hours before admission 8 hour turnaround time
Unscheduled deliveries: Tested in triage | 2 hour turnaround time
All women asked about possible COVID-19 symptoms at time of admission
Management protocols
Positive test: Managed in a dedicated COVID-19 unit
Asymptomatic: Managed on routine labor floor | Health care workers used PPE until the test result available
Patients and one allowed support person received procedure masks on arrival
Support persons screened for symptoms but not tested
RESULTS:
Total of 635 pregnant
Test results
Positive for SARS-CoV-2: 3.6% (23 women)
Positive but asymptomatic on presentation: 43.5% (10 women)
Symptoms on presentation
Reported symptoms on presentation: 3.3% (21 women)
Positive for COVID-19: 61.9% (13 women)
Did not report symptoms on presentation: 96.7% (614 women)
Positive for COVID-19: 1.6% (10 women)
CONCLUSION:
Symptoms alone did not reliably identify pregnant women with COVID-19 on admission to labor and delivery units
In this study, positive test rates were higher than those reported in the general population, leading the authors to suggest that infection rates in the general population, where testing is generally limited to symptomatic patients, may be higher
Sutton et al. (NEJM, 2020) in a similar paper also found a much higher prevalence of infection with universal screening of pregnant women admitted for delivery in NYC
215 pregnant women (all were screened)
Symptomatic: 1.9% | All were positive on testing
Asymptomatic women: 99.5% | 13.7% positive on testing
87.9% of women had no symptoms of Covid-19 at presentation
The authors in the NEJM paper conclude that
The potential benefits of a universal testing approach include the ability to use Covid-19 status to determine hospital isolation practices and bed assignments, inform neonatal care, and guide the use of personal protective equipment
Access to such clinical data provides an important opportunity to protect mothers, babies, and health care teams during these challenging times
Point-of-Care Test for Preeclampsia: Glycosylated Fibronectin
BACKGROUND AND PURPOSE:
Glycosylated fibronectin (GlyFn) is a biomarker that has potential as a point-of-care (POC) diagnostic test for preeclampsia (PE) | Could be of particular benefit in low resource regions
Elevated GlyFn with PE may be related to differential glycosylation due to oxidative stress in PE
Nagalla et al. (BJOG, 2020) assessed the performance of GlyFn POC test for PE in a large Southeast Asian cohort vs biomarkers currently available and in use
METHODS:
Prospective case-control study
Setting
India
Participants
Pregnant women at ≥20 weeks
Normotensive and protein/creatinine ratio <0.3
PE: Hypertension and protein/creatinine ratio ≥0.3
Gestational hypertension: Hypertension and protein/creatinine ratio <0.3
Study design
GlyFn levels were determined using a POC device
Current marker levels, i.e. PIGF, sFlt-1, and PAPPA2 were determined by immunoassay
Logistic regression modelling and receiver-operating characteristic (ROC) curves were used to assess performance
PPv and NPV reported at specific thresholds
RESULTS:
Total of 798 pregnant women
Normotensive: 469
PE: 135
Gestational hypertension: 194
All patients were being evaluated for new onset hypertension | Prevalence of PE: 17%
The following were significantly associated with clinically defined PE (P<0.01)
Increased levels of GlyFn: Area under the ROC (AUROC) 0.99 (95% CI, 0.98 to 0.99)
Increased levels of sFlt-1: AUROC 0.86 (95% CI, 0.83 to 0.89)
Increased levels of PAPPA2: AUROC 0.96 (95% CI, 0.94 to 0.97)
Decreased levels of PlGF: AUROC 0.96 (95% CI, 0.94 to 0.98)
Patients with gestational hypertension
48% were positive for more than two PE biomarkers
70% of these delivered preterm
NPVs and PPVs for GlyFn
NPV: >99% regardless of PE prevalence (at 5%, 7% and 17%)
PPV: ranged depending on prevalence from from 42% (5% prevalence) to 74% (17% prevalence seen in this study)
CONCLUSION:
The use of the GlyFn POC test in a low/middle-income country was validated for PE diagnosis
Overall, all the biomarkers studied demonstrated good test performance for the diagnosis of PE, with GlynFn exhibiting superior discriminatory results
Further studies required in asymptomatic population prior to using GlynFn as a broad based screening test
Cochrane Review 2020: Are Progestogen-Releasing IUDs Effective for Managing Heavy Menstrual Bleeding?
BACKGROUND AND PURPOSE:
Use of the levonorgestrel-releasing intrauterine system (LNG-IUS) can reduce menstrual blood loss by up to 90%
Bofill Rodriguez et al. (Cochrane Systematic Review – Intervention, 2020) determined the effectiveness, patient acceptability, and safety of progestogen-releasing intrauterine systems to reduce heavy menstrual bleeding (HMB)
METHODS:
Systematic review and meta-analysis
Inclusion criteria
RCTs
Trials in women of reproductive age treated with LNG-IUS devices vs
No treatment | Placebo | Other medical/surgical therapy for HMB
Study design and data analysis
Two authors independently extracted data, assessed risk of bias and determined certainty of evidence using GRADE criteria
RESULTS:
25 RCTs were included | Combined total of 2511 women
LNG-IUS vs Other Medical Therapy
Other therapies investigated were
Norethisterone acetate
Medroxyprogesterone acetate
Oral contraceptive pill
Mefenamic acid
Tranexamic acid
Usual medical treatment (patient choice of suitable oral treatment)
The LNG-IUS may improve HMB, with lower menstrual blood loss using various bleeding assessment tools
The alkaline hematin method: Mean difference (MD) 66.91 mL (95% CI, 42.61 to 91.20; 2 studies, 170 women; low‐certainty evidence)
The Pictorial Bleeding Assessment Chart: MD 55.05 (95% CI 27.83 to 82.28; 3 studies, 335 women; low‐certainty evidence)
Uncertain whether the LNG-IUS has any effect on women’s satisfaction up to one year
RR 1.28 (95% CI 1.01 to 1.63; 3 studies, 141 women; very low‐certainty evidence)
The LNG‐IUS probably leads to slightly higher quality of life compared with other medical therapy using the following scales
The SF‐36: MD 2.90 (95% CI, 0.06 to 5.74; 1 study: 571 women; moderate‐certainty evidence)
The Menorrhagia Multi-Attribute Scale: MD 13.40 (95% CI, 9.89 to 16.91; 1 trial, 571 women; moderate‐certainty evidence)
Serious adverse events were similar between LNG-IUS and other medical therapies
RR 0.91 (95% CI 0.63 to 1.30; 1 study, 571 women; moderate‐certainty evidence)
Compared to LNG-IUS, women using other medical therapy are probably more likely to
Withdraw from treatment for any reasons; RR 0.49 (95% CI, 0.39 to 0.60; 1 study, 571 women, moderate‐certainty evidence)
Experience treatment failure: RR 0.34 (95% CI 0.26 to 0.44; 6 studies, 535 women; moderate‐certainty evidence)
LNG‐IUS vs Endometrial Resection or Ablation (EA)
Bleeding outcome results are inconsistent
Effect of LNG-IUS vs EA are probably similar when comparing rates for the following
Amenorrhea | Hypomenorrhea | Eumenorrhea
Uncertain whether there is a difference in quality of life
Women with the LNG-IUS are probably more likely to have any adverse event
OBG Project CME requires a modern web browser (Internet Explorer 10+, Mozilla Firefox, Apple Safari, Google Chrome, Microsoft Edge). Certain educational activities may require additional software to view multimedia, presentation, or printable versions of their content. These activities will be marked as such and will provide links to the required software. That software may be: Adobe Flash, Apple QuickTime, Adobe Acrobat, Microsoft PowerPoint, Windows Media Player, or Real Networks Real One Player.
Disclosure of Unlabeled Use
This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.
The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.
Disclaimer
Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information
presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
Jointly provided by
NOT ENOUGH CME HOURS
It appears you don't have enough CME Hours to take this Post-Test. Feel free to buy additional CME hours or upgrade your current CME subscription plan
You are now leaving the ObG website and on your way to PRIORITY at UCSF, an independent website. Therefore, we are not responsible for the content or availability of this site