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FDA approves certolizumab label update for pregnancy, breastfeeding
The manufacturer of certolizumab pegol, UCB, announced March 22 that the Food and Drug Administration approved a label update to the biologic that includes pharmacokinetic data showing negligible to low transfer of the biologic through the placenta and minimal mother-to-infant transfer from breast milk.
In the CRIB study, certolizumab levels were below the lower limit of quantification (defined as 0.032 mcg/mL) in 13 out of 15 infant blood samples at birth and in all samples at weeks 4 and 8. No anticertolizumab antibodies were detected in mothers, umbilical cords, or infants.
In the CRADLE study, 56% of 137 breast milk samples from 17 mothers had no measurable certolizumab, and the remaining samples showed minimal levels of the biologic. No serious adverse reactions were noted in the 17 infants in the study.
“It is well recognized that women with chronic inflammatory disease face uncertainty during motherhood given the lack of information on treatment during pregnancy and breastfeeding. Many women with chronic inflammatory disease discontinue their biologic treatment during pregnancy, often when they need disease control the most,” said CRADLE lead study author Megan E. B. Clowse, MD, of Duke University, Durham, N.C., in a press release issued by UCB. “These data for Cimzia provide important information to empower women and healthcare providers making decisions about treatment during pregnancy and breastfeeding.”
UCB said that limited data from an ongoing pregnancy registry regarding the use of certolizumab in pregnant women are not sufficient to inform a risk of major birth defects or other adverse pregnancy outcomes.
The manufacturer of certolizumab pegol, UCB, announced March 22 that the Food and Drug Administration approved a label update to the biologic that includes pharmacokinetic data showing negligible to low transfer of the biologic through the placenta and minimal mother-to-infant transfer from breast milk.
In the CRIB study, certolizumab levels were below the lower limit of quantification (defined as 0.032 mcg/mL) in 13 out of 15 infant blood samples at birth and in all samples at weeks 4 and 8. No anticertolizumab antibodies were detected in mothers, umbilical cords, or infants.
In the CRADLE study, 56% of 137 breast milk samples from 17 mothers had no measurable certolizumab, and the remaining samples showed minimal levels of the biologic. No serious adverse reactions were noted in the 17 infants in the study.
“It is well recognized that women with chronic inflammatory disease face uncertainty during motherhood given the lack of information on treatment during pregnancy and breastfeeding. Many women with chronic inflammatory disease discontinue their biologic treatment during pregnancy, often when they need disease control the most,” said CRADLE lead study author Megan E. B. Clowse, MD, of Duke University, Durham, N.C., in a press release issued by UCB. “These data for Cimzia provide important information to empower women and healthcare providers making decisions about treatment during pregnancy and breastfeeding.”
UCB said that limited data from an ongoing pregnancy registry regarding the use of certolizumab in pregnant women are not sufficient to inform a risk of major birth defects or other adverse pregnancy outcomes.
The manufacturer of certolizumab pegol, UCB, announced March 22 that the Food and Drug Administration approved a label update to the biologic that includes pharmacokinetic data showing negligible to low transfer of the biologic through the placenta and minimal mother-to-infant transfer from breast milk.
In the CRIB study, certolizumab levels were below the lower limit of quantification (defined as 0.032 mcg/mL) in 13 out of 15 infant blood samples at birth and in all samples at weeks 4 and 8. No anticertolizumab antibodies were detected in mothers, umbilical cords, or infants.
In the CRADLE study, 56% of 137 breast milk samples from 17 mothers had no measurable certolizumab, and the remaining samples showed minimal levels of the biologic. No serious adverse reactions were noted in the 17 infants in the study.
“It is well recognized that women with chronic inflammatory disease face uncertainty during motherhood given the lack of information on treatment during pregnancy and breastfeeding. Many women with chronic inflammatory disease discontinue their biologic treatment during pregnancy, often when they need disease control the most,” said CRADLE lead study author Megan E. B. Clowse, MD, of Duke University, Durham, N.C., in a press release issued by UCB. “These data for Cimzia provide important information to empower women and healthcare providers making decisions about treatment during pregnancy and breastfeeding.”
UCB said that limited data from an ongoing pregnancy registry regarding the use of certolizumab in pregnant women are not sufficient to inform a risk of major birth defects or other adverse pregnancy outcomes.
Maternal biologic therapy does not affect infant vaccine responses
MAUI, HAWAII – The infants of inflammatory bowel disease patients on biologic therapy during pregnancy and breastfeeding do not have a diminished response rate to the inactivated vaccines routinely given during the first 6 months of life, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
“Those babies are going to have detectable levels of drug on board, but they respond to vaccines just as well as infants born to mothers with IBD who were not on biologic therapy. The rates are the same, albeit lower than in the general population,” according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.
Previous reports from the national registry have established that continuation of biologics in IBD patients throughout pregnancy and breastfeeding to maintain disease control poses no increased risks to the fetus in terms of rates of congenital anomalies, spontaneous abortion, intrauterine growth restriction, low birth weight, or longer-term developmental delay, compared with unexposed babies whose mothers have IBD.
Dr. Ananthakrishnan’s analysis focused on response rates to tetanus and Haemophilus influenzae B vaccines in the infants of 179 PIANO patients. Sixty-five percent of the IBD patients were on various biologic agents during pregnancy, 8% were on a thiopurine, 21% were on combination therapy, and 6% weren’t exposed to any IBD medications. Serologic studies showed that there was no difference across the four groups in terms of infant rates of protective titers in response to the vaccines. However, the 69%-84% rates of protective titers in the four groups fell short of the 90%-plus rate expected in the general population.
Live virus vaccines are contraindicated in the first 6 months of life in infants exposed to maternal biologics in utero. The only live virus vaccine given during that time frame in the United States is rotavirus, administered at months 2 and 3. Dr. Mahadevan and others recommend skipping that vaccine in babies exposed in utero to any IBD biologic other than certolizumab pegol (Cimzia), which uniquely doesn’t cross the placenta.
“That being said, infants born to 71 of our PIANO participants on anti-TNF therapy in pregnancy inadvertently got the rotavirus vaccine, and they were all just fine, even with very high drug levels,” the gastroenterologist said.
The live virus varicella and MMR vaccines can safely be given as scheduled at 1 year of age. By that time the biologics are long gone from the child.
Dr. Mahadevan reported receiving research funding from the Crohn’s and Colitis Foundation of America, which sponsors the PIANO registry. She also has financial relationships with several pharmaceutical companies.
MAUI, HAWAII – The infants of inflammatory bowel disease patients on biologic therapy during pregnancy and breastfeeding do not have a diminished response rate to the inactivated vaccines routinely given during the first 6 months of life, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
“Those babies are going to have detectable levels of drug on board, but they respond to vaccines just as well as infants born to mothers with IBD who were not on biologic therapy. The rates are the same, albeit lower than in the general population,” according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.
Previous reports from the national registry have established that continuation of biologics in IBD patients throughout pregnancy and breastfeeding to maintain disease control poses no increased risks to the fetus in terms of rates of congenital anomalies, spontaneous abortion, intrauterine growth restriction, low birth weight, or longer-term developmental delay, compared with unexposed babies whose mothers have IBD.
Dr. Ananthakrishnan’s analysis focused on response rates to tetanus and Haemophilus influenzae B vaccines in the infants of 179 PIANO patients. Sixty-five percent of the IBD patients were on various biologic agents during pregnancy, 8% were on a thiopurine, 21% were on combination therapy, and 6% weren’t exposed to any IBD medications. Serologic studies showed that there was no difference across the four groups in terms of infant rates of protective titers in response to the vaccines. However, the 69%-84% rates of protective titers in the four groups fell short of the 90%-plus rate expected in the general population.
Live virus vaccines are contraindicated in the first 6 months of life in infants exposed to maternal biologics in utero. The only live virus vaccine given during that time frame in the United States is rotavirus, administered at months 2 and 3. Dr. Mahadevan and others recommend skipping that vaccine in babies exposed in utero to any IBD biologic other than certolizumab pegol (Cimzia), which uniquely doesn’t cross the placenta.
“That being said, infants born to 71 of our PIANO participants on anti-TNF therapy in pregnancy inadvertently got the rotavirus vaccine, and they were all just fine, even with very high drug levels,” the gastroenterologist said.
The live virus varicella and MMR vaccines can safely be given as scheduled at 1 year of age. By that time the biologics are long gone from the child.
Dr. Mahadevan reported receiving research funding from the Crohn’s and Colitis Foundation of America, which sponsors the PIANO registry. She also has financial relationships with several pharmaceutical companies.
MAUI, HAWAII – The infants of inflammatory bowel disease patients on biologic therapy during pregnancy and breastfeeding do not have a diminished response rate to the inactivated vaccines routinely given during the first 6 months of life, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
“Those babies are going to have detectable levels of drug on board, but they respond to vaccines just as well as infants born to mothers with IBD who were not on biologic therapy. The rates are the same, albeit lower than in the general population,” according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.
Previous reports from the national registry have established that continuation of biologics in IBD patients throughout pregnancy and breastfeeding to maintain disease control poses no increased risks to the fetus in terms of rates of congenital anomalies, spontaneous abortion, intrauterine growth restriction, low birth weight, or longer-term developmental delay, compared with unexposed babies whose mothers have IBD.
Dr. Ananthakrishnan’s analysis focused on response rates to tetanus and Haemophilus influenzae B vaccines in the infants of 179 PIANO patients. Sixty-five percent of the IBD patients were on various biologic agents during pregnancy, 8% were on a thiopurine, 21% were on combination therapy, and 6% weren’t exposed to any IBD medications. Serologic studies showed that there was no difference across the four groups in terms of infant rates of protective titers in response to the vaccines. However, the 69%-84% rates of protective titers in the four groups fell short of the 90%-plus rate expected in the general population.
Live virus vaccines are contraindicated in the first 6 months of life in infants exposed to maternal biologics in utero. The only live virus vaccine given during that time frame in the United States is rotavirus, administered at months 2 and 3. Dr. Mahadevan and others recommend skipping that vaccine in babies exposed in utero to any IBD biologic other than certolizumab pegol (Cimzia), which uniquely doesn’t cross the placenta.
“That being said, infants born to 71 of our PIANO participants on anti-TNF therapy in pregnancy inadvertently got the rotavirus vaccine, and they were all just fine, even with very high drug levels,” the gastroenterologist said.
The live virus varicella and MMR vaccines can safely be given as scheduled at 1 year of age. By that time the biologics are long gone from the child.
Dr. Mahadevan reported receiving research funding from the Crohn’s and Colitis Foundation of America, which sponsors the PIANO registry. She also has financial relationships with several pharmaceutical companies.
EXPERT ANALYSIS FROM RWCS 2018
Docs worry there’s ‘nowhere to send’ new and expectant moms with depression
Lawmakers in California will begin debate next month on a bill that would require doctors to screen new moms for mental health problems – once while they’re pregnant and again after they give birth.
But many obstetricians and pediatricians bristle at the idea, saying they are afraid to screen new moms for depression and anxiety.
“What are you going to do with those people who screen positive?” asked Laura L. Sirott, MD, an ob.gyn. who practices in Pasadena. “Some providers have nowhere to send them.”
Nationally, depression affects up to one in seven women during or after pregnancy, according to the American Psychological Association.
And, of women who screen positive for the condition, 78% don’t get mental health treatment, according to a 2015 research review published in the journal Obstetrics & Gynecology.
Dr. Sirott said her patients give a range of reasons why they don’t take her up on a referral to a psychologist: “ ‘Oh, they don’t take my insurance.’ Or ‘my insurance pays for three visits.’ ‘I can’t take time off work to go to those visits.’ ‘It’s a 3-month wait to get in to that person.’ ”
She said it’s also hard to find a psychiatrist who is willing to treat them and who is trained in the complexities of prescribing medications to pregnant or breastfeeding women, especially in rural areas.
“So it’s very frustrating,” Dr. Sirott said, “to ask patients about a problem and then not have any way to solve that problem.”
Moms are frustrated, too. After the baby comes, no one asks about the baby’s mother anymore.
Wendy Root Askew struggled for years to get pregnant, and when she finally did, her anxiety got worse. She couldn’t stop worrying that something would go wrong.
“And then, after I had my son, I would have these dreams where someone would come to the door and they would say, ‘Well, you know, we’re just going to wait 2 weeks to see if you get to keep your baby or not,’ ” Ms. Root Askew said. “And it really impacted my ability to bond with him.”
She likes California’s bill, AB 2193, because it goes beyond mandated screening. It would require health insurance companies to set up case management programs to help moms find a therapist, and connect obstetricians or pediatricians to a psychiatric specialist.
“Just like we have case-management programs for patients who have diabetes or sleep issues or back pain, a case-management program requires the insurance company to take some ownership of making sure their patients are getting the treatment they need to be healthy,” said Ms. Root Askew, who is now advocating for the bill on behalf of the group 2020 Mom.
Health insurance companies haven’t taken a position on the legislation. It’s unclear how much it would cost them to comply, because some already have infrastructure in place for case-management programs, and some do not. But there is consensus among insurers and health advocates that such programs save money in the long run.
“The sooner that you can get good treatment for a mom, the less expensive that condition will be to manage over the course of the woman’s life and over the course of that child’s life,” Ms. Root Askew said.
Some doctors still have their objections. Under the bill, they could be disciplined for not screening. Some have said they worry about how much time it would take.
The health care system, and the incentives, aren’t set up for this sort of screening, Dr. Sirott said.
“Currently, I get $6 for screening a patient,” she said. “By the time I put it on a piece of paper and print it, it’s not worth it.”
It’s not clear whether the direct and indirect costs of screening would be worth it to the patients, either. Four other states – Illinois, Massachusetts, New Jersey, and West Virginia – have tried mandated screening, and it did not result in more women getting treatment, according to a 2015 study published in Psychiatric Services.
Even with California’s extra requirement that insurance companies facilitate care, women could still face high copays or limits on the number of therapy sessions. Or, a new mother might be so overwhelmed with care for her newborn that it would be difficult to add anything to her busy schedule.
What does seem to work, according to the study of mandated screening in other states, is when nurses or mental health providers visit new moms at home.
“Despite abundant goodwill, there is no evidence that state policies are addressing this great need,” the study’s authors report.
Supporters of California’s proposed bill, however, say doctors need to start somewhere. Screening is the first step in recognizing the full scope of the problem, said Nirmaljit Dhami, MD, a Mountain View, Calif., psychiatrist. Women should be screened on an ongoing basis throughout pregnancy and for a year after birth, Dr. Dhami said, not just once or twice as the bill requires.
“I often tell doctors that if you don’t know that somebody is suicidal, it doesn’t mean that their suicidality will go away,” she said. “If you don’t ask, the risk is the same.”
This story is part of a partnership that includes KQED, NPR, and Kaiser Health News. KHN’s coverage of women’s health care issues is supported in part by The David and Lucile Packard Foundation. KHN is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
Lawmakers in California will begin debate next month on a bill that would require doctors to screen new moms for mental health problems – once while they’re pregnant and again after they give birth.
But many obstetricians and pediatricians bristle at the idea, saying they are afraid to screen new moms for depression and anxiety.
“What are you going to do with those people who screen positive?” asked Laura L. Sirott, MD, an ob.gyn. who practices in Pasadena. “Some providers have nowhere to send them.”
Nationally, depression affects up to one in seven women during or after pregnancy, according to the American Psychological Association.
And, of women who screen positive for the condition, 78% don’t get mental health treatment, according to a 2015 research review published in the journal Obstetrics & Gynecology.
Dr. Sirott said her patients give a range of reasons why they don’t take her up on a referral to a psychologist: “ ‘Oh, they don’t take my insurance.’ Or ‘my insurance pays for three visits.’ ‘I can’t take time off work to go to those visits.’ ‘It’s a 3-month wait to get in to that person.’ ”
She said it’s also hard to find a psychiatrist who is willing to treat them and who is trained in the complexities of prescribing medications to pregnant or breastfeeding women, especially in rural areas.
“So it’s very frustrating,” Dr. Sirott said, “to ask patients about a problem and then not have any way to solve that problem.”
Moms are frustrated, too. After the baby comes, no one asks about the baby’s mother anymore.
Wendy Root Askew struggled for years to get pregnant, and when she finally did, her anxiety got worse. She couldn’t stop worrying that something would go wrong.
“And then, after I had my son, I would have these dreams where someone would come to the door and they would say, ‘Well, you know, we’re just going to wait 2 weeks to see if you get to keep your baby or not,’ ” Ms. Root Askew said. “And it really impacted my ability to bond with him.”
She likes California’s bill, AB 2193, because it goes beyond mandated screening. It would require health insurance companies to set up case management programs to help moms find a therapist, and connect obstetricians or pediatricians to a psychiatric specialist.
“Just like we have case-management programs for patients who have diabetes or sleep issues or back pain, a case-management program requires the insurance company to take some ownership of making sure their patients are getting the treatment they need to be healthy,” said Ms. Root Askew, who is now advocating for the bill on behalf of the group 2020 Mom.
Health insurance companies haven’t taken a position on the legislation. It’s unclear how much it would cost them to comply, because some already have infrastructure in place for case-management programs, and some do not. But there is consensus among insurers and health advocates that such programs save money in the long run.
“The sooner that you can get good treatment for a mom, the less expensive that condition will be to manage over the course of the woman’s life and over the course of that child’s life,” Ms. Root Askew said.
Some doctors still have their objections. Under the bill, they could be disciplined for not screening. Some have said they worry about how much time it would take.
The health care system, and the incentives, aren’t set up for this sort of screening, Dr. Sirott said.
“Currently, I get $6 for screening a patient,” she said. “By the time I put it on a piece of paper and print it, it’s not worth it.”
It’s not clear whether the direct and indirect costs of screening would be worth it to the patients, either. Four other states – Illinois, Massachusetts, New Jersey, and West Virginia – have tried mandated screening, and it did not result in more women getting treatment, according to a 2015 study published in Psychiatric Services.
Even with California’s extra requirement that insurance companies facilitate care, women could still face high copays or limits on the number of therapy sessions. Or, a new mother might be so overwhelmed with care for her newborn that it would be difficult to add anything to her busy schedule.
What does seem to work, according to the study of mandated screening in other states, is when nurses or mental health providers visit new moms at home.
“Despite abundant goodwill, there is no evidence that state policies are addressing this great need,” the study’s authors report.
Supporters of California’s proposed bill, however, say doctors need to start somewhere. Screening is the first step in recognizing the full scope of the problem, said Nirmaljit Dhami, MD, a Mountain View, Calif., psychiatrist. Women should be screened on an ongoing basis throughout pregnancy and for a year after birth, Dr. Dhami said, not just once or twice as the bill requires.
“I often tell doctors that if you don’t know that somebody is suicidal, it doesn’t mean that their suicidality will go away,” she said. “If you don’t ask, the risk is the same.”
This story is part of a partnership that includes KQED, NPR, and Kaiser Health News. KHN’s coverage of women’s health care issues is supported in part by The David and Lucile Packard Foundation. KHN is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
Lawmakers in California will begin debate next month on a bill that would require doctors to screen new moms for mental health problems – once while they’re pregnant and again after they give birth.
But many obstetricians and pediatricians bristle at the idea, saying they are afraid to screen new moms for depression and anxiety.
“What are you going to do with those people who screen positive?” asked Laura L. Sirott, MD, an ob.gyn. who practices in Pasadena. “Some providers have nowhere to send them.”
Nationally, depression affects up to one in seven women during or after pregnancy, according to the American Psychological Association.
And, of women who screen positive for the condition, 78% don’t get mental health treatment, according to a 2015 research review published in the journal Obstetrics & Gynecology.
Dr. Sirott said her patients give a range of reasons why they don’t take her up on a referral to a psychologist: “ ‘Oh, they don’t take my insurance.’ Or ‘my insurance pays for three visits.’ ‘I can’t take time off work to go to those visits.’ ‘It’s a 3-month wait to get in to that person.’ ”
She said it’s also hard to find a psychiatrist who is willing to treat them and who is trained in the complexities of prescribing medications to pregnant or breastfeeding women, especially in rural areas.
“So it’s very frustrating,” Dr. Sirott said, “to ask patients about a problem and then not have any way to solve that problem.”
Moms are frustrated, too. After the baby comes, no one asks about the baby’s mother anymore.
Wendy Root Askew struggled for years to get pregnant, and when she finally did, her anxiety got worse. She couldn’t stop worrying that something would go wrong.
“And then, after I had my son, I would have these dreams where someone would come to the door and they would say, ‘Well, you know, we’re just going to wait 2 weeks to see if you get to keep your baby or not,’ ” Ms. Root Askew said. “And it really impacted my ability to bond with him.”
She likes California’s bill, AB 2193, because it goes beyond mandated screening. It would require health insurance companies to set up case management programs to help moms find a therapist, and connect obstetricians or pediatricians to a psychiatric specialist.
“Just like we have case-management programs for patients who have diabetes or sleep issues or back pain, a case-management program requires the insurance company to take some ownership of making sure their patients are getting the treatment they need to be healthy,” said Ms. Root Askew, who is now advocating for the bill on behalf of the group 2020 Mom.
Health insurance companies haven’t taken a position on the legislation. It’s unclear how much it would cost them to comply, because some already have infrastructure in place for case-management programs, and some do not. But there is consensus among insurers and health advocates that such programs save money in the long run.
“The sooner that you can get good treatment for a mom, the less expensive that condition will be to manage over the course of the woman’s life and over the course of that child’s life,” Ms. Root Askew said.
Some doctors still have their objections. Under the bill, they could be disciplined for not screening. Some have said they worry about how much time it would take.
The health care system, and the incentives, aren’t set up for this sort of screening, Dr. Sirott said.
“Currently, I get $6 for screening a patient,” she said. “By the time I put it on a piece of paper and print it, it’s not worth it.”
It’s not clear whether the direct and indirect costs of screening would be worth it to the patients, either. Four other states – Illinois, Massachusetts, New Jersey, and West Virginia – have tried mandated screening, and it did not result in more women getting treatment, according to a 2015 study published in Psychiatric Services.
Even with California’s extra requirement that insurance companies facilitate care, women could still face high copays or limits on the number of therapy sessions. Or, a new mother might be so overwhelmed with care for her newborn that it would be difficult to add anything to her busy schedule.
What does seem to work, according to the study of mandated screening in other states, is when nurses or mental health providers visit new moms at home.
“Despite abundant goodwill, there is no evidence that state policies are addressing this great need,” the study’s authors report.
Supporters of California’s proposed bill, however, say doctors need to start somewhere. Screening is the first step in recognizing the full scope of the problem, said Nirmaljit Dhami, MD, a Mountain View, Calif., psychiatrist. Women should be screened on an ongoing basis throughout pregnancy and for a year after birth, Dr. Dhami said, not just once or twice as the bill requires.
“I often tell doctors that if you don’t know that somebody is suicidal, it doesn’t mean that their suicidality will go away,” she said. “If you don’t ask, the risk is the same.”
This story is part of a partnership that includes KQED, NPR, and Kaiser Health News. KHN’s coverage of women’s health care issues is supported in part by The David and Lucile Packard Foundation. KHN is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
Balance risk with reality for pre-conception diabetic counseling
CHICAGO – In particular, “several retrospective studies have shown that the risk for congenital malformations is increased with higher hemoglobin A1c levels,” said Susan Kirk, MD, speaking at a “Meet the Professor” session at the annual meeting of the Endocrine Society.
However, pointed out Dr. Kirk, fact-based counseling about pregnancy risks for women with type 1 or type 2 diabetes can – and should – occur within the framework of a strong and accepting physician-patient relationship.
Most women with diabetes have received pre-conception counseling about the risks of pregnancy with diabetes and the importance of glycemic control. “Despite that, I think many of us are often surprised by the percentage of unplanned pregnancies,” said Dr. Kirk, of the University of Virginia, Charlottesville, in an interview.
“What I have learned is that the desire to become pregnant is so strong, and the contemplation of all the adverse events that can happen … is really scary, not only to the woman but to her partner as well.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Kirk continued, “The more compassion you can show, and the more emphasis that you can place on the fact that she’s most likely to have a healthy baby, the chances are she’ll work with you from the beginning to get her control where she needs to be.”
Target numbers for hemoglobin A1c have become lower over the past several years, with the American Diabetes Association now recommending pre-conception levels below 6.5%. “There’s no randomized controlled trial that defines what that ideal number should be, but with the passage of time and some larger studies, we now know that ‘as close to normal as possible’ should be the goal,” Dr. Kirk said. This means that if women can tolerate the lower blood glucose levels without serious symptoms of hypoglycemia, a level of less than 6% is more preferable still, she said.
In terms of medication management for women with diabetes who become pregnant, physicians need to think about angiotensin converting enzyme inhibitors and statins, both of which are contraindicated for use during pregnancy. If a patient is pregnant or trying for a pregnancy, “I will stop those, and either leave them off all medicine entirely, or transition them to something that’s safe for use during pregnancy,” said Dr. Kirk.
It’s important to know if women have any microvascular complications because these are likely to progress during pregnancy, said Dr. Kirk. “The good news is, it all goes back to where she started before pregnancy after she has the baby,” though pre-existing advanced renal disease or eye disease may still cause concern for permanent damage. “If there are changes in the back of the eye that are suggestive of proliferative retinopathy, she should absolutely try to get that taken care of before she gets pregnant.”
The use of prenatal vitamins is another area where strong evidence is lacking, said Dr. Kirk. What is known is the folic acid supplementation “has been proven beyond a doubt to lower the rate of neural tube complications. And it’s cheap, and it’s easy to take. So any woman who’s even hinting at getting pregnant should be placed on those,” she said.
Dr. Kirk had no financial disclosures.
SOURCE: Kirk S. ENDO 2018, Session M-02-3.
CHICAGO – In particular, “several retrospective studies have shown that the risk for congenital malformations is increased with higher hemoglobin A1c levels,” said Susan Kirk, MD, speaking at a “Meet the Professor” session at the annual meeting of the Endocrine Society.
However, pointed out Dr. Kirk, fact-based counseling about pregnancy risks for women with type 1 or type 2 diabetes can – and should – occur within the framework of a strong and accepting physician-patient relationship.
Most women with diabetes have received pre-conception counseling about the risks of pregnancy with diabetes and the importance of glycemic control. “Despite that, I think many of us are often surprised by the percentage of unplanned pregnancies,” said Dr. Kirk, of the University of Virginia, Charlottesville, in an interview.
“What I have learned is that the desire to become pregnant is so strong, and the contemplation of all the adverse events that can happen … is really scary, not only to the woman but to her partner as well.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Kirk continued, “The more compassion you can show, and the more emphasis that you can place on the fact that she’s most likely to have a healthy baby, the chances are she’ll work with you from the beginning to get her control where she needs to be.”
Target numbers for hemoglobin A1c have become lower over the past several years, with the American Diabetes Association now recommending pre-conception levels below 6.5%. “There’s no randomized controlled trial that defines what that ideal number should be, but with the passage of time and some larger studies, we now know that ‘as close to normal as possible’ should be the goal,” Dr. Kirk said. This means that if women can tolerate the lower blood glucose levels without serious symptoms of hypoglycemia, a level of less than 6% is more preferable still, she said.
In terms of medication management for women with diabetes who become pregnant, physicians need to think about angiotensin converting enzyme inhibitors and statins, both of which are contraindicated for use during pregnancy. If a patient is pregnant or trying for a pregnancy, “I will stop those, and either leave them off all medicine entirely, or transition them to something that’s safe for use during pregnancy,” said Dr. Kirk.
It’s important to know if women have any microvascular complications because these are likely to progress during pregnancy, said Dr. Kirk. “The good news is, it all goes back to where she started before pregnancy after she has the baby,” though pre-existing advanced renal disease or eye disease may still cause concern for permanent damage. “If there are changes in the back of the eye that are suggestive of proliferative retinopathy, she should absolutely try to get that taken care of before she gets pregnant.”
The use of prenatal vitamins is another area where strong evidence is lacking, said Dr. Kirk. What is known is the folic acid supplementation “has been proven beyond a doubt to lower the rate of neural tube complications. And it’s cheap, and it’s easy to take. So any woman who’s even hinting at getting pregnant should be placed on those,” she said.
Dr. Kirk had no financial disclosures.
SOURCE: Kirk S. ENDO 2018, Session M-02-3.
CHICAGO – In particular, “several retrospective studies have shown that the risk for congenital malformations is increased with higher hemoglobin A1c levels,” said Susan Kirk, MD, speaking at a “Meet the Professor” session at the annual meeting of the Endocrine Society.
However, pointed out Dr. Kirk, fact-based counseling about pregnancy risks for women with type 1 or type 2 diabetes can – and should – occur within the framework of a strong and accepting physician-patient relationship.
Most women with diabetes have received pre-conception counseling about the risks of pregnancy with diabetes and the importance of glycemic control. “Despite that, I think many of us are often surprised by the percentage of unplanned pregnancies,” said Dr. Kirk, of the University of Virginia, Charlottesville, in an interview.
“What I have learned is that the desire to become pregnant is so strong, and the contemplation of all the adverse events that can happen … is really scary, not only to the woman but to her partner as well.”
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Dr. Kirk continued, “The more compassion you can show, and the more emphasis that you can place on the fact that she’s most likely to have a healthy baby, the chances are she’ll work with you from the beginning to get her control where she needs to be.”
Target numbers for hemoglobin A1c have become lower over the past several years, with the American Diabetes Association now recommending pre-conception levels below 6.5%. “There’s no randomized controlled trial that defines what that ideal number should be, but with the passage of time and some larger studies, we now know that ‘as close to normal as possible’ should be the goal,” Dr. Kirk said. This means that if women can tolerate the lower blood glucose levels without serious symptoms of hypoglycemia, a level of less than 6% is more preferable still, she said.
In terms of medication management for women with diabetes who become pregnant, physicians need to think about angiotensin converting enzyme inhibitors and statins, both of which are contraindicated for use during pregnancy. If a patient is pregnant or trying for a pregnancy, “I will stop those, and either leave them off all medicine entirely, or transition them to something that’s safe for use during pregnancy,” said Dr. Kirk.
It’s important to know if women have any microvascular complications because these are likely to progress during pregnancy, said Dr. Kirk. “The good news is, it all goes back to where she started before pregnancy after she has the baby,” though pre-existing advanced renal disease or eye disease may still cause concern for permanent damage. “If there are changes in the back of the eye that are suggestive of proliferative retinopathy, she should absolutely try to get that taken care of before she gets pregnant.”
The use of prenatal vitamins is another area where strong evidence is lacking, said Dr. Kirk. What is known is the folic acid supplementation “has been proven beyond a doubt to lower the rate of neural tube complications. And it’s cheap, and it’s easy to take. So any woman who’s even hinting at getting pregnant should be placed on those,” she said.
Dr. Kirk had no financial disclosures.
SOURCE: Kirk S. ENDO 2018, Session M-02-3.
REPORTING FROM ENDO 2018
Adding biomarkers beats NICE guidelines for detecting preeclampsia
FROM ULTRASOUND IN OBSTETRICS & GYNECOLOGY
Screening for preeclampsia using the United Kingdom’s National Institute for Health and Care Excellence (NICE) guidelines detects only about one-third of cases, according to a study published in Ultrasound in Obstetrics & Gynecology.
The United Kingdom-based prospective multicenter study, involving 16,747 singleton pregnancies, also looked at the effectiveness of a screening method that used Bayes’ theorem to combine maternal risk factors with biomarkers.
Preeclampsia developed in 473 (2.8%) pregnancies, and in 142 cases (0.8%) this led to preterm birth.
The NICE method of screening labels as high-risk women who have one major risk factor – such as a history of hypertensive disease in pregnancy or chronic kidney disease – or two moderate factors, including first pregnancy older than 40 years or a family history of preeclampsia.
This method of screening detected 30.4% of the cases of preeclampsia that developed and 40.8% of the cases that resulted in pre-term birth. The overall screen-positive rate by the NICE method was 10.3% of all participants in the study (1,727 women).
The Bayes’ theorem-based method assessed maternal risk factors in combination with mean arterial pressure and serum pregnancy-associated plasma protein-A. The detection rate for all preeclampsia using this method was 42.5%, representing an improvement of 11.3% over the NICE method, after adjusting for the effects of aspirin use in both groups. Researchers also examined the effect of adding in the biomarkers of uterine artery pulsatility index and serum placental growth factor, and found this detected 82.4% of preterm preeclampsia.
“The performance of screening by a combination of maternal factors with biomarkers was far superior to that of screening by NICE guidelines,” wrote Min Yi Tan, MD, of King’s College Hospital in London, and co-authors.
Overall, 4.5% of women in the study took aspirin from 14 weeks’ gestation until 36 weeks or delivery, but only 23.2% of women who screened positive according to the NICE guidelines took aspirin.
“Such poor compliance may at least in part be attributed to the generally held belief, based on the results of a meta-analysis in 2007, that aspirin reduces the risk of PE by only about 10%,” Dr. Tan and co-authors wrote.
The authors acknowledged that their study did not explore the health economic implications of the combined screening approach, but said there was now accumulating evidence that the performance of first-trimester screening for preterm preeclampsia could be improved substantially by the additional measurement of biomarkers.The study was sponsored by King’s College London, and supported by the National Institute for Health Research Efficacy and Mechanism Evaluation Programme, the Fetal Medicine Foundation and NIHR Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital NHS Foundation Trust, with in-kind support from PerkinElmer Life and Analytical Sciences, and Thermo Fisher Scientific. No conflicts of interest were declared.
[email protected]
SOURCE: Tan MY et al. Ultrasound Obstet & Gynecol. 2018 Mar 14. doi: 10.1002/uog.19039.
FROM ULTRASOUND IN OBSTETRICS & GYNECOLOGY
Screening for preeclampsia using the United Kingdom’s National Institute for Health and Care Excellence (NICE) guidelines detects only about one-third of cases, according to a study published in Ultrasound in Obstetrics & Gynecology.
The United Kingdom-based prospective multicenter study, involving 16,747 singleton pregnancies, also looked at the effectiveness of a screening method that used Bayes’ theorem to combine maternal risk factors with biomarkers.
Preeclampsia developed in 473 (2.8%) pregnancies, and in 142 cases (0.8%) this led to preterm birth.
The NICE method of screening labels as high-risk women who have one major risk factor – such as a history of hypertensive disease in pregnancy or chronic kidney disease – or two moderate factors, including first pregnancy older than 40 years or a family history of preeclampsia.
This method of screening detected 30.4% of the cases of preeclampsia that developed and 40.8% of the cases that resulted in pre-term birth. The overall screen-positive rate by the NICE method was 10.3% of all participants in the study (1,727 women).
The Bayes’ theorem-based method assessed maternal risk factors in combination with mean arterial pressure and serum pregnancy-associated plasma protein-A. The detection rate for all preeclampsia using this method was 42.5%, representing an improvement of 11.3% over the NICE method, after adjusting for the effects of aspirin use in both groups. Researchers also examined the effect of adding in the biomarkers of uterine artery pulsatility index and serum placental growth factor, and found this detected 82.4% of preterm preeclampsia.
“The performance of screening by a combination of maternal factors with biomarkers was far superior to that of screening by NICE guidelines,” wrote Min Yi Tan, MD, of King’s College Hospital in London, and co-authors.
Overall, 4.5% of women in the study took aspirin from 14 weeks’ gestation until 36 weeks or delivery, but only 23.2% of women who screened positive according to the NICE guidelines took aspirin.
“Such poor compliance may at least in part be attributed to the generally held belief, based on the results of a meta-analysis in 2007, that aspirin reduces the risk of PE by only about 10%,” Dr. Tan and co-authors wrote.
The authors acknowledged that their study did not explore the health economic implications of the combined screening approach, but said there was now accumulating evidence that the performance of first-trimester screening for preterm preeclampsia could be improved substantially by the additional measurement of biomarkers.The study was sponsored by King’s College London, and supported by the National Institute for Health Research Efficacy and Mechanism Evaluation Programme, the Fetal Medicine Foundation and NIHR Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital NHS Foundation Trust, with in-kind support from PerkinElmer Life and Analytical Sciences, and Thermo Fisher Scientific. No conflicts of interest were declared.
[email protected]
SOURCE: Tan MY et al. Ultrasound Obstet & Gynecol. 2018 Mar 14. doi: 10.1002/uog.19039.
FROM ULTRASOUND IN OBSTETRICS & GYNECOLOGY
Screening for preeclampsia using the United Kingdom’s National Institute for Health and Care Excellence (NICE) guidelines detects only about one-third of cases, according to a study published in Ultrasound in Obstetrics & Gynecology.
The United Kingdom-based prospective multicenter study, involving 16,747 singleton pregnancies, also looked at the effectiveness of a screening method that used Bayes’ theorem to combine maternal risk factors with biomarkers.
Preeclampsia developed in 473 (2.8%) pregnancies, and in 142 cases (0.8%) this led to preterm birth.
The NICE method of screening labels as high-risk women who have one major risk factor – such as a history of hypertensive disease in pregnancy or chronic kidney disease – or two moderate factors, including first pregnancy older than 40 years or a family history of preeclampsia.
This method of screening detected 30.4% of the cases of preeclampsia that developed and 40.8% of the cases that resulted in pre-term birth. The overall screen-positive rate by the NICE method was 10.3% of all participants in the study (1,727 women).
The Bayes’ theorem-based method assessed maternal risk factors in combination with mean arterial pressure and serum pregnancy-associated plasma protein-A. The detection rate for all preeclampsia using this method was 42.5%, representing an improvement of 11.3% over the NICE method, after adjusting for the effects of aspirin use in both groups. Researchers also examined the effect of adding in the biomarkers of uterine artery pulsatility index and serum placental growth factor, and found this detected 82.4% of preterm preeclampsia.
“The performance of screening by a combination of maternal factors with biomarkers was far superior to that of screening by NICE guidelines,” wrote Min Yi Tan, MD, of King’s College Hospital in London, and co-authors.
Overall, 4.5% of women in the study took aspirin from 14 weeks’ gestation until 36 weeks or delivery, but only 23.2% of women who screened positive according to the NICE guidelines took aspirin.
“Such poor compliance may at least in part be attributed to the generally held belief, based on the results of a meta-analysis in 2007, that aspirin reduces the risk of PE by only about 10%,” Dr. Tan and co-authors wrote.
The authors acknowledged that their study did not explore the health economic implications of the combined screening approach, but said there was now accumulating evidence that the performance of first-trimester screening for preterm preeclampsia could be improved substantially by the additional measurement of biomarkers.The study was sponsored by King’s College London, and supported by the National Institute for Health Research Efficacy and Mechanism Evaluation Programme, the Fetal Medicine Foundation and NIHR Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital NHS Foundation Trust, with in-kind support from PerkinElmer Life and Analytical Sciences, and Thermo Fisher Scientific. No conflicts of interest were declared.
[email protected]
SOURCE: Tan MY et al. Ultrasound Obstet & Gynecol. 2018 Mar 14. doi: 10.1002/uog.19039.
Key clinical point: Screening for preeclampsia using the United Kingdom’s National Institute for Health and Care Excellence (NICE) guidelines only detects around one-third of all preeclampsia cases, but the addition of biomarkers can improve this significantly.
Major finding: The NICE guidelines detected 30.4% of cases of preeclampsia, while a Bayes’ theorem-based method using maternal risk factors and biomarkers detected 42.5%.
Data source: A prospective multicenter study of 16,747 singleton pregnancies.
Disclosures: The study was sponsored by King’s College London, and supported by the National Institute for Health Research Efficacy and Mechanism Evaluation Programme, the Fetal Medicine Foundation and NIHR Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital NHS Foundation Trust, with in-kind support from PerkinElmer Life and Analytical Sciences, and Thermo Fisher Scientific. No conflicts of interest were declared.
Source: Tan MY et al. Ultrasound Obstet & Gynecol. 2018 Mar 14. doi: 10.1002/uog.19039.
mainbar
Screening for preeclampsia using the United Kingdom’s National Institute for Health and Care Excellence (NICE) guidelines detects only about one-third of cases, according to a study published in Ultrasound in Obstetrics & Gynecology.
The United Kingdom-based prospective multicenter study, involving 16,747 singleton pregnancies, also looked at the effectiveness of a screening method that used Bayes’ theorem to combine maternal risk factors with biomarkers.
Preeclampsia developed in 473 (2.8%) pregnancies, and in 142 cases (0.8%) this led to preterm birth.
The NICE method of screening labels as high-risk women who have one major risk factor – such as a history of hypertensive disease in pregnancy or chronic kidney disease – or two moderate factors, including first pregnancy older than 40 years or a family history of preeclampsia.
This method of screening detected 30.4% of the cases of preeclampsia that developed and 40.8% of the cases that resulted in pre-term birth. The overall screen-positive rate by the NICE method was 10.3% of all participants in the study (1,727 women).
The Bayes’ theorem-based method assessed maternal risk factors in combination with mean arterial pressure and serum pregnancy-associated plasma protein-A. The detection rate for all preeclampsia using this method was 42.5%, representing an improvement of 11.3% over the NICE method, after adjusting for the effects of aspirin use in both groups. Researchers also examined the effect of adding in the biomarkers of uterine artery pulsatility index and serum placental growth factor, and found this detected 82.4% of preterm preeclampsia.
“The performance of screening by a combination of maternal factors with biomarkers was far superior to that of screening by NICE guidelines,” wrote Min Yi Tan, MD, of King’s College Hospital in London, and co-authors.
Overall, 4.5% of women in the study took aspirin from 14 weeks’ gestation until 36 weeks or delivery, but only 23.2% of women who screened positive according to the NICE guidelines took aspirin.
“Such poor compliance may at least in part be attributed to the generally held belief, based on the results of a meta-analysis in 2007, that aspirin reduces the risk of PE by only about 10%,” Dr. Tan and co-authors wrote.
The authors acknowledged that their study did not explore the health economic implications of the combined screening approach, but said there was now accumulating evidence that the performance of first-trimester screening for preterm preeclampsia could be improved substantially by the additional measurement of biomarkers.
The study was sponsored by King’s College London, and supported by the National Institute for Health Research Efficacy and Mechanism Evaluation Programme, the Fetal Medicine Foundation and NIHR Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital NHS Foundation Trust, with in-kind support from PerkinElmer Life and Analytical Sciences, and Thermo Fisher Scientific. No conflicts of interest were declared.
SOURCE: Tan MY et al. Ultrasound Obstet & Gynecol. 2018 Mar 14. doi: 10.1002/uog.19039.
Bariatric surgery may adversely affect newborns
Bariatric surgery can offer a variety of benefits to mothers and improve neonatal outcomes but also offers substantial risk, according to a systematic literature review.
“Bariatric surgery, with patients matched for presurgery body mass index [BMI], resulted in a reduction in gestational diabetes mellitus, large-for-gestational-age infants, large babies (composite of large for gestational age and macrosomia), gestational hypertension, all hypertensive disorders, postpartum hemorrhage, and cesarean delivery rates,” wrote Wilson Kwong, MD, of the University of Toronto, and his colleagues. “However, there was an increase in small-for-gestational age infants, intrauterine growth restriction, small babies (composite of small for gestational age and intrauterine growth restriction), and preterm deliveries.”
Dr. Kwong and his research team developed this study to investigate the benefits and risks of bariatric surgery on neonatal outcomes. They designed a systematic review that involved a literature search of 2,616 abstracts using MEDLINE, Embase, Cochrane, Web of Science, and PubMed. They searched all from initiation of the databases to Dec. 12, 2016. Ultimately, this yielded 20 cohort studies and approximately 2.8 million subjects for review and meta-analysis. From this data, pooled odds ratios were estimated, as well as the number needed to benefit (NNTB) and the number need to harm (NNTH) to display the pooled absolute risk difference.
The results of the primary analysis, in which BMIs were similar between control subjects and the presurgery BMIs of women receiving treatment, yielded positives for mothers who underwent bariatric surgery and their newborns. As stated by Dr. Kwong and his research team, newborns were less likely to be large-for-gestational-age babies or deal with macrosomia (odds ratio, 0.36; 95% confidence interval, 0.20-0.66; NNTB, 7) and mothers were less likely to experience hypertensive disorders (OR, 0.38; 95% CI, 0.27-0.53, NNTB, 8) and postpartum hemorrhage (OR, 0.32; 95% CI, 0.08-1.37; NNTB, 9).
Despite the positives, the risk for harm was higher in a number of outcomes. Babies were more likely to be small for gestational age, have intrauterine growth restriction (OR, 2.16; 95% CI, 1.34-3.48; NNTH, 21) ,and be delivered preterm (OR, 1.35; 95% CI, 1.02-1.79; NNTH, 35).
A secondary analysis revealed that malabsorptive surgeries resulted in a significantly greater decrease (P = .012) in large babies (OR, 0.28; 95% CI, 0.22-0.36), compared with restrictive surgeries (OR, 0.50; 95% CI, 0.35-0.73). This analysis also revealed that malabsorptive bariatric surgeries corresponded to an increase in the number of small babies (OR, 2.39; 95% CI, 1.94-2.94; P = .023).
The increased risk of smaller babies may be caused by micronutrient deficiencies in pregnancy, according to Dr. Kwong. Nutritional deficiencies are reported in up to 80% of bariatric surgery patients, malabsorptive patients in particular.
“Common nutrient deficiencies after bariatric surgery include protein, B vitamins, fat-soluble vitamins, essential fatty acids, and minerals (zinc and copper), which may persist throughout pregnancy,” wrote Dr. Kwong and his colleagues.
Similar nutrient deficiencies have been identified in a case study of a woman who underwent a duodenal switch published in the Journal of Obstetrics & Gynaecology Canada. After several failed pregnancies from complications from malnutrition, the patient presented herself to physicians 10 weeks into her next pregnancy and was found to be deficient in vitamins A, D, E, and K, and minerals iron and zinc. After supplementation with a daily nutritional drink containing vitamins and protein, her vitamin levels were near normal at week 24. She eventually delivered a healthy newborn with normal-appearing features. The researchers from this study recommended that patients seeking bariatric surgery should avoid malabsorptive surgeries and defer to less extreme surgical methods.
A strength of the systematic review was the matching of studies based on presurgery and prepregnancy BMI. This was a departure from previous studies that combined all studies. Additionally, this study compared the outcomes based on the type of data source that was used. Despite these strengths, the design and results of the studies in the analysis limited the results of the review. None of the included studies were randomized; instead, they consisted of observational cohort studies, which are prone for confounding by indication.
“In counseling patients of childbearing potential who are interested in pursuing bariatric surgery, a discussion of both possible benefits and risks on pregnancy outcomes must take place,” cautioned Dr. Kwong and his associates. “Future studies should explore the causes of these potential adverse pregnancy outcomes and develop strategies that may prevent them.”
All authors affiliated with the study had no relevant financial conflicts of interest to report.
SOURCE: Kwong W et al. Am J Obstet Gynecol. 2018 Feb 15. doi: 10.1016/j.ajog.2018.02.003.
Bariatric surgery can offer a variety of benefits to mothers and improve neonatal outcomes but also offers substantial risk, according to a systematic literature review.
“Bariatric surgery, with patients matched for presurgery body mass index [BMI], resulted in a reduction in gestational diabetes mellitus, large-for-gestational-age infants, large babies (composite of large for gestational age and macrosomia), gestational hypertension, all hypertensive disorders, postpartum hemorrhage, and cesarean delivery rates,” wrote Wilson Kwong, MD, of the University of Toronto, and his colleagues. “However, there was an increase in small-for-gestational age infants, intrauterine growth restriction, small babies (composite of small for gestational age and intrauterine growth restriction), and preterm deliveries.”
Dr. Kwong and his research team developed this study to investigate the benefits and risks of bariatric surgery on neonatal outcomes. They designed a systematic review that involved a literature search of 2,616 abstracts using MEDLINE, Embase, Cochrane, Web of Science, and PubMed. They searched all from initiation of the databases to Dec. 12, 2016. Ultimately, this yielded 20 cohort studies and approximately 2.8 million subjects for review and meta-analysis. From this data, pooled odds ratios were estimated, as well as the number needed to benefit (NNTB) and the number need to harm (NNTH) to display the pooled absolute risk difference.
The results of the primary analysis, in which BMIs were similar between control subjects and the presurgery BMIs of women receiving treatment, yielded positives for mothers who underwent bariatric surgery and their newborns. As stated by Dr. Kwong and his research team, newborns were less likely to be large-for-gestational-age babies or deal with macrosomia (odds ratio, 0.36; 95% confidence interval, 0.20-0.66; NNTB, 7) and mothers were less likely to experience hypertensive disorders (OR, 0.38; 95% CI, 0.27-0.53, NNTB, 8) and postpartum hemorrhage (OR, 0.32; 95% CI, 0.08-1.37; NNTB, 9).
Despite the positives, the risk for harm was higher in a number of outcomes. Babies were more likely to be small for gestational age, have intrauterine growth restriction (OR, 2.16; 95% CI, 1.34-3.48; NNTH, 21) ,and be delivered preterm (OR, 1.35; 95% CI, 1.02-1.79; NNTH, 35).
A secondary analysis revealed that malabsorptive surgeries resulted in a significantly greater decrease (P = .012) in large babies (OR, 0.28; 95% CI, 0.22-0.36), compared with restrictive surgeries (OR, 0.50; 95% CI, 0.35-0.73). This analysis also revealed that malabsorptive bariatric surgeries corresponded to an increase in the number of small babies (OR, 2.39; 95% CI, 1.94-2.94; P = .023).
The increased risk of smaller babies may be caused by micronutrient deficiencies in pregnancy, according to Dr. Kwong. Nutritional deficiencies are reported in up to 80% of bariatric surgery patients, malabsorptive patients in particular.
“Common nutrient deficiencies after bariatric surgery include protein, B vitamins, fat-soluble vitamins, essential fatty acids, and minerals (zinc and copper), which may persist throughout pregnancy,” wrote Dr. Kwong and his colleagues.
Similar nutrient deficiencies have been identified in a case study of a woman who underwent a duodenal switch published in the Journal of Obstetrics & Gynaecology Canada. After several failed pregnancies from complications from malnutrition, the patient presented herself to physicians 10 weeks into her next pregnancy and was found to be deficient in vitamins A, D, E, and K, and minerals iron and zinc. After supplementation with a daily nutritional drink containing vitamins and protein, her vitamin levels were near normal at week 24. She eventually delivered a healthy newborn with normal-appearing features. The researchers from this study recommended that patients seeking bariatric surgery should avoid malabsorptive surgeries and defer to less extreme surgical methods.
A strength of the systematic review was the matching of studies based on presurgery and prepregnancy BMI. This was a departure from previous studies that combined all studies. Additionally, this study compared the outcomes based on the type of data source that was used. Despite these strengths, the design and results of the studies in the analysis limited the results of the review. None of the included studies were randomized; instead, they consisted of observational cohort studies, which are prone for confounding by indication.
“In counseling patients of childbearing potential who are interested in pursuing bariatric surgery, a discussion of both possible benefits and risks on pregnancy outcomes must take place,” cautioned Dr. Kwong and his associates. “Future studies should explore the causes of these potential adverse pregnancy outcomes and develop strategies that may prevent them.”
All authors affiliated with the study had no relevant financial conflicts of interest to report.
SOURCE: Kwong W et al. Am J Obstet Gynecol. 2018 Feb 15. doi: 10.1016/j.ajog.2018.02.003.
Bariatric surgery can offer a variety of benefits to mothers and improve neonatal outcomes but also offers substantial risk, according to a systematic literature review.
“Bariatric surgery, with patients matched for presurgery body mass index [BMI], resulted in a reduction in gestational diabetes mellitus, large-for-gestational-age infants, large babies (composite of large for gestational age and macrosomia), gestational hypertension, all hypertensive disorders, postpartum hemorrhage, and cesarean delivery rates,” wrote Wilson Kwong, MD, of the University of Toronto, and his colleagues. “However, there was an increase in small-for-gestational age infants, intrauterine growth restriction, small babies (composite of small for gestational age and intrauterine growth restriction), and preterm deliveries.”
Dr. Kwong and his research team developed this study to investigate the benefits and risks of bariatric surgery on neonatal outcomes. They designed a systematic review that involved a literature search of 2,616 abstracts using MEDLINE, Embase, Cochrane, Web of Science, and PubMed. They searched all from initiation of the databases to Dec. 12, 2016. Ultimately, this yielded 20 cohort studies and approximately 2.8 million subjects for review and meta-analysis. From this data, pooled odds ratios were estimated, as well as the number needed to benefit (NNTB) and the number need to harm (NNTH) to display the pooled absolute risk difference.
The results of the primary analysis, in which BMIs were similar between control subjects and the presurgery BMIs of women receiving treatment, yielded positives for mothers who underwent bariatric surgery and their newborns. As stated by Dr. Kwong and his research team, newborns were less likely to be large-for-gestational-age babies or deal with macrosomia (odds ratio, 0.36; 95% confidence interval, 0.20-0.66; NNTB, 7) and mothers were less likely to experience hypertensive disorders (OR, 0.38; 95% CI, 0.27-0.53, NNTB, 8) and postpartum hemorrhage (OR, 0.32; 95% CI, 0.08-1.37; NNTB, 9).
Despite the positives, the risk for harm was higher in a number of outcomes. Babies were more likely to be small for gestational age, have intrauterine growth restriction (OR, 2.16; 95% CI, 1.34-3.48; NNTH, 21) ,and be delivered preterm (OR, 1.35; 95% CI, 1.02-1.79; NNTH, 35).
A secondary analysis revealed that malabsorptive surgeries resulted in a significantly greater decrease (P = .012) in large babies (OR, 0.28; 95% CI, 0.22-0.36), compared with restrictive surgeries (OR, 0.50; 95% CI, 0.35-0.73). This analysis also revealed that malabsorptive bariatric surgeries corresponded to an increase in the number of small babies (OR, 2.39; 95% CI, 1.94-2.94; P = .023).
The increased risk of smaller babies may be caused by micronutrient deficiencies in pregnancy, according to Dr. Kwong. Nutritional deficiencies are reported in up to 80% of bariatric surgery patients, malabsorptive patients in particular.
“Common nutrient deficiencies after bariatric surgery include protein, B vitamins, fat-soluble vitamins, essential fatty acids, and minerals (zinc and copper), which may persist throughout pregnancy,” wrote Dr. Kwong and his colleagues.
Similar nutrient deficiencies have been identified in a case study of a woman who underwent a duodenal switch published in the Journal of Obstetrics & Gynaecology Canada. After several failed pregnancies from complications from malnutrition, the patient presented herself to physicians 10 weeks into her next pregnancy and was found to be deficient in vitamins A, D, E, and K, and minerals iron and zinc. After supplementation with a daily nutritional drink containing vitamins and protein, her vitamin levels were near normal at week 24. She eventually delivered a healthy newborn with normal-appearing features. The researchers from this study recommended that patients seeking bariatric surgery should avoid malabsorptive surgeries and defer to less extreme surgical methods.
A strength of the systematic review was the matching of studies based on presurgery and prepregnancy BMI. This was a departure from previous studies that combined all studies. Additionally, this study compared the outcomes based on the type of data source that was used. Despite these strengths, the design and results of the studies in the analysis limited the results of the review. None of the included studies were randomized; instead, they consisted of observational cohort studies, which are prone for confounding by indication.
“In counseling patients of childbearing potential who are interested in pursuing bariatric surgery, a discussion of both possible benefits and risks on pregnancy outcomes must take place,” cautioned Dr. Kwong and his associates. “Future studies should explore the causes of these potential adverse pregnancy outcomes and develop strategies that may prevent them.”
All authors affiliated with the study had no relevant financial conflicts of interest to report.
SOURCE: Kwong W et al. Am J Obstet Gynecol. 2018 Feb 15. doi: 10.1016/j.ajog.2018.02.003.
FROM THE AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY
Key clinical point: Bariatric surgery can offer a variety of benefits to mothers and improve neonatal outcomes but also offers substantial risk.
Major finding: Babies were more likely to be small (OR, 2.16; 95% CI, 1.34-3.48; number needed to harm, 21) and be delivered preterm (OR, 1.35; 95% CI, 1.02-1.79; NNTH, 35).
Study details: A systematic literature search of 20 cohort studies and approximately 2.8 million subjects using MEDLINE, Embase, Cochrane, Web of Science, and PubMed from the date of the databases’ inception to Dec. 12, 2016.
Disclosures: All authors affiliated with the study had no relevant financial conflicts of interest to report.
Source: Kwong W et al. Am J Obstet Gynecol. 2018 Feb 15. doi: 10.1016/j.ajog.2018.02.003.
Does Fish Oil During Pregnancy Help Prevent Asthma in Kids?
A 24-year-old G2P1 at 24 weeks’ gestation presents to your clinic for a routine prenatal visit. Her older daughter has asthma, and she wants to know if there is anything she can do to reduce her second child’s risk for it. What do you recommend?
Asthma is the most common chronic disease in children in resource-rich countries such as the United States.2 According to the CDC, 8.4% of children were diagnosed with asthma in 2015.3
Omega-3 fatty acids, found naturally in fish oil, are thought to confer anti-inflammatory properties that offer protection against asthma. Clinical trials have shown that fish oil supplementation in pregnancy results in higher levels of omega-3 fatty acids, along with anti-inflammatory changes, in offspring.4 Previous epidemiologic studies have also found that consumption of omega-3 fatty acids decreases the risk for atopy and asthma in offspring.5,6
A Cochrane review published in 2015, however, concluded that omega-3 supplementation during pregnancy had no benefit on wheeze or asthma in offspring.7 Five RCTs were included in the analysis. The largest trial, by Palmer et al, which included 706 women, showed no benefit for supplementation.8 The second largest, by Olsen et al, which included 533 women, did show a benefit (hazard ratio [HR], 0.37; number needed to treat [NNT], 19.6).9
These results, however, were limited by heterogeneity in the amount of fish oil supplemented and duration of follow-up. For example, the children in the Palmer study were followed only until age 3, which is around the time that asthma can be formally diagnosed—potentially leading to underreporting.8 In addition, the diagnosis of asthma was based on parent report of three episodes of wheezing, use of daily asthma medication, or use of a national registry—all of which can underestimate the incidence of asthma. The reported rate of childhood asthma with IgE-sensitization (rate without sensitization was not reported) was 1.8% in both study groups—much lower than the CDC’s rate of 8.4%, suggesting underdiagnosis.3,8 Due to these biases and other potential confounders, no firm conclusions can be drawn from the Cochrane review.
STUDY SUMMARY
Maternal fish oil supplementation reduces asthma in children
This single-center, double-blind RCT of 736 pregnant women evaluated the effect of 2.4 g/d of n-3 long-chain polyunsaturated fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) or placebo (olive oil), starting at an estimated gestational age of 24 to 26 weeks, on wheeze or asthma incidence in their offspring.1
Eligible women were between 22 and 26 weeks’ pregnant at the time of recruitment. Exclusion criteria included supplementation of 600 IU/d or more of vitamin D, or having any endocrine, cardiac, or renal disorders. The investigators randomized the women in a 1:1 ratio to either fish oil or placebo. Maternal EPA and DHA blood levels were tested at the time of randomization and one week after birth.
The primary outcome was persistent wheeze or asthma (after age 3, persistent wheeze was termed asthma), determined based on daily diary recordings of five episodes of troublesome lung symptoms within the past six months (each lasting for at least three consecutive days); rescue use of inhaled ß2-agonists; and/or relapse after a three-month course of inhaled glucocorticoids. Secondary outcomes included reduced incidence of respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization.
In total, 695 offspring were included in the study, with 95.5% follow-up at three years and 93.1% at five. The children had scheduled pediatric visits at 1 week; at one, three, six, 12, 18, 24, 30, and 36 months; and at 4 and 5 years. They also had acute visits for any pulmonary, allergic, or dermatologic symptoms that arose.
Results. The investigators found that the children of mothers who took fish oil had a lower risk for persistent wheeze or asthma at ages 3 to 5, compared to those who received placebo (16.9% vs 23.7%; HR, 0.69; NNT, 14.7). But this effect was significant only in the children whose mothers had baseline EPA and DHA levels in the lowest third (17.5% vs 34.1%; HR, 0.46; NNT, 5.6). Similarly, fish oil supplementation had a greater benefit in children whose mothers had consumed the least EPA and DHA before the start of the study (18.5% vs 32.4%; HR, 0.55; NNT, 7.2).
As for the secondary outcomes, only a reduction in lower respiratory infections was associated with fish oil supplementation compared with placebo (38.8% vs 45.5%; HR, 0.77; NNT, 14.9). There was no reduction in asthma exacerbations, eczema, or risk for sensitization in the fish oil group.
WHAT’S NEW?
Study adds fuel to the fire
This study strengthens the case for fish oil supplementation during pregnancy to reduce the risk for asthma in offspring, despite the recent Cochrane review that showed no benefit.1,7 The Palmer study used a much lower amount of omega-3s (900 mg/d fish oil vs 2,400 mg/d in the current trial).1,8 Olsen et al supplemented with a greater amount of omega-3s (2,700 mg/d) and did find a benefit.9 The NNT from the Olsen study (19.6) is consistent with that of the current investigation, suggesting that a higher dosage may be necessary to prevent the onset of asthma.
Additionally, this study followed children for a longer period than did the Palmer study, which may have led to more accurate diagnoses of asthma.1,8 Lastly, the diagnosis of asthma in the Palmer study was based on parent survey data and use of daily asthma medicine rather than on daily diary cards, which are often more accurate.
Consider fish consumption. Both this study and the Olsen trial were performed in Denmark.1,9 While Denmark and the United States have had a relatively similar level of fish consumption since the 1990s, women in Denmark may eat a higher proportion of oily fish than women in the United States, given the more common inclusion of mackerel and herring in their diet.10 Thus, the effect of supplementation may be more pronounced in women in the US.
CAVEATS
Ideal dose? Which women to treat?
The FDA currently recommends 8 to 12 oz of fish per week for pregnant women, but there are no guidelines on the ideal amount of fish oil to be consumed.11 The Palmer study, using 900 mg/d of fish oil, did not show a benefit, whereas there did appear to be a benefit in this study (2,400 mg/d) and the Olsen study (2,700 mg/d).1,8,9 Further research is needed to determine the optimal dosage.
The decreased risk for persistent wheeze or asthma was seen only in the children of women whose EPA and DHA blood levels were in the lowest third of the study population. Thus, only women whose blood levels are low to begin with will likely benefit from this intervention. Currently, EPA and DHA levels are not routinely checked, but there may be some benefit to doing so.
One proxy for blood levels is maternal intake of fish at baseline. The investigators found that there was an association between dietary intake of fish and blood levels of EPA and DHA (r, 0.32).1 Therefore, additional screening questions to gauge fish consumption would be useful to identify women most likely to benefit from supplementation.
CHALLENGES TO IMPLEMENTATION
Multiple pills, additional cost
Since omega-3 fatty acids are relatively safe and the NNT in the general population is low, it may be worth supplementing all pregnant women, even without a commercially available blood test for EPA or DHA. Nevertheless, some women may find it challenging to take up to four additional pills per day for 13 or more weeks. Also, there is an associated cost with these supplements, although it is low.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018;67[2]: 100-102).
1. Bisgaard H, Stokholm J, Chawes BL, et al. Fish oil-derived fatty acids in pregnancy and wheeze and asthma in offspring. N Engl J Med. 2016;375(26):2530-2539.
2. Masoli M, Fabian D, Holt S, et al. The global burden of asthma: executive summary of the GINA Dissemination Committee Report. Allergy. 2004;59(5):469-478.
3. CDC . Asthma. www.cdc.gov/asthma/most_recent_data.htm. Accessed February 1, 2018.
4. Miyata J, Arita M. Role of omega-3 fatty acids and their metabolites in asthma and allergic diseases. Allergol Int. 2015;64(1):27-34.
5. Salam MT, Li YF, Langholz B, et al. Maternal fish consumption during pregnancy and risk of early childhood asthma. J Asthma. 2005;42(6):513-518.
6. Calvani M, Alessandri C, Sopo SM, et al. Consumption of fish, butter and margarine during pregnancy and development of allergic sensitizations in the offspring: role of maternal atopy. Pediatr Allergy Immunol. 2006;17(2):94-102.
7. Gunaratne AW, Makrides M, Collins CT. Maternal prenatal and/or postnatal n-3 long chain polyunsaturated fatty acids (LCPUFA) supplementation for preventing allergies in early childhood. Cochrane Database Syst Rev. 2015;22(7): CD010085.
8. Palmer D, Sullivan T, Gold M, et al. Randomized controlled trial of fish oil supplementation in pregnancy on childhood allergies. Allergy. 2013;68:1370-1376.
9. Olsen SF, Østerdal ML, Salvig JD, et al. Fish oil intake compared with olive oil intake in late pregnancy and asthma in the offspring: 16 y of registry-based follow-up from a randomized controlled trial. Am J Clin Nutr. 2008;88(1): 167-175.
10. Helgi Library. Fish consumption per capita by country. www.helgilibrary.com/indicators/fish-consumption-per-capita/. Accessed February 1, 2018.
11. FDA Advice About Eating Fish, From the Environmental Protection Agency and Food and Drug Administration; Revised Fish Advice; Availability. Fed Regist. 2017;82:6571-6574.
A 24-year-old G2P1 at 24 weeks’ gestation presents to your clinic for a routine prenatal visit. Her older daughter has asthma, and she wants to know if there is anything she can do to reduce her second child’s risk for it. What do you recommend?
Asthma is the most common chronic disease in children in resource-rich countries such as the United States.2 According to the CDC, 8.4% of children were diagnosed with asthma in 2015.3
Omega-3 fatty acids, found naturally in fish oil, are thought to confer anti-inflammatory properties that offer protection against asthma. Clinical trials have shown that fish oil supplementation in pregnancy results in higher levels of omega-3 fatty acids, along with anti-inflammatory changes, in offspring.4 Previous epidemiologic studies have also found that consumption of omega-3 fatty acids decreases the risk for atopy and asthma in offspring.5,6
A Cochrane review published in 2015, however, concluded that omega-3 supplementation during pregnancy had no benefit on wheeze or asthma in offspring.7 Five RCTs were included in the analysis. The largest trial, by Palmer et al, which included 706 women, showed no benefit for supplementation.8 The second largest, by Olsen et al, which included 533 women, did show a benefit (hazard ratio [HR], 0.37; number needed to treat [NNT], 19.6).9
These results, however, were limited by heterogeneity in the amount of fish oil supplemented and duration of follow-up. For example, the children in the Palmer study were followed only until age 3, which is around the time that asthma can be formally diagnosed—potentially leading to underreporting.8 In addition, the diagnosis of asthma was based on parent report of three episodes of wheezing, use of daily asthma medication, or use of a national registry—all of which can underestimate the incidence of asthma. The reported rate of childhood asthma with IgE-sensitization (rate without sensitization was not reported) was 1.8% in both study groups—much lower than the CDC’s rate of 8.4%, suggesting underdiagnosis.3,8 Due to these biases and other potential confounders, no firm conclusions can be drawn from the Cochrane review.
STUDY SUMMARY
Maternal fish oil supplementation reduces asthma in children
This single-center, double-blind RCT of 736 pregnant women evaluated the effect of 2.4 g/d of n-3 long-chain polyunsaturated fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) or placebo (olive oil), starting at an estimated gestational age of 24 to 26 weeks, on wheeze or asthma incidence in their offspring.1
Eligible women were between 22 and 26 weeks’ pregnant at the time of recruitment. Exclusion criteria included supplementation of 600 IU/d or more of vitamin D, or having any endocrine, cardiac, or renal disorders. The investigators randomized the women in a 1:1 ratio to either fish oil or placebo. Maternal EPA and DHA blood levels were tested at the time of randomization and one week after birth.
The primary outcome was persistent wheeze or asthma (after age 3, persistent wheeze was termed asthma), determined based on daily diary recordings of five episodes of troublesome lung symptoms within the past six months (each lasting for at least three consecutive days); rescue use of inhaled ß2-agonists; and/or relapse after a three-month course of inhaled glucocorticoids. Secondary outcomes included reduced incidence of respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization.
In total, 695 offspring were included in the study, with 95.5% follow-up at three years and 93.1% at five. The children had scheduled pediatric visits at 1 week; at one, three, six, 12, 18, 24, 30, and 36 months; and at 4 and 5 years. They also had acute visits for any pulmonary, allergic, or dermatologic symptoms that arose.
Results. The investigators found that the children of mothers who took fish oil had a lower risk for persistent wheeze or asthma at ages 3 to 5, compared to those who received placebo (16.9% vs 23.7%; HR, 0.69; NNT, 14.7). But this effect was significant only in the children whose mothers had baseline EPA and DHA levels in the lowest third (17.5% vs 34.1%; HR, 0.46; NNT, 5.6). Similarly, fish oil supplementation had a greater benefit in children whose mothers had consumed the least EPA and DHA before the start of the study (18.5% vs 32.4%; HR, 0.55; NNT, 7.2).
As for the secondary outcomes, only a reduction in lower respiratory infections was associated with fish oil supplementation compared with placebo (38.8% vs 45.5%; HR, 0.77; NNT, 14.9). There was no reduction in asthma exacerbations, eczema, or risk for sensitization in the fish oil group.
WHAT’S NEW?
Study adds fuel to the fire
This study strengthens the case for fish oil supplementation during pregnancy to reduce the risk for asthma in offspring, despite the recent Cochrane review that showed no benefit.1,7 The Palmer study used a much lower amount of omega-3s (900 mg/d fish oil vs 2,400 mg/d in the current trial).1,8 Olsen et al supplemented with a greater amount of omega-3s (2,700 mg/d) and did find a benefit.9 The NNT from the Olsen study (19.6) is consistent with that of the current investigation, suggesting that a higher dosage may be necessary to prevent the onset of asthma.
Additionally, this study followed children for a longer period than did the Palmer study, which may have led to more accurate diagnoses of asthma.1,8 Lastly, the diagnosis of asthma in the Palmer study was based on parent survey data and use of daily asthma medicine rather than on daily diary cards, which are often more accurate.
Consider fish consumption. Both this study and the Olsen trial were performed in Denmark.1,9 While Denmark and the United States have had a relatively similar level of fish consumption since the 1990s, women in Denmark may eat a higher proportion of oily fish than women in the United States, given the more common inclusion of mackerel and herring in their diet.10 Thus, the effect of supplementation may be more pronounced in women in the US.
CAVEATS
Ideal dose? Which women to treat?
The FDA currently recommends 8 to 12 oz of fish per week for pregnant women, but there are no guidelines on the ideal amount of fish oil to be consumed.11 The Palmer study, using 900 mg/d of fish oil, did not show a benefit, whereas there did appear to be a benefit in this study (2,400 mg/d) and the Olsen study (2,700 mg/d).1,8,9 Further research is needed to determine the optimal dosage.
The decreased risk for persistent wheeze or asthma was seen only in the children of women whose EPA and DHA blood levels were in the lowest third of the study population. Thus, only women whose blood levels are low to begin with will likely benefit from this intervention. Currently, EPA and DHA levels are not routinely checked, but there may be some benefit to doing so.
One proxy for blood levels is maternal intake of fish at baseline. The investigators found that there was an association between dietary intake of fish and blood levels of EPA and DHA (r, 0.32).1 Therefore, additional screening questions to gauge fish consumption would be useful to identify women most likely to benefit from supplementation.
CHALLENGES TO IMPLEMENTATION
Multiple pills, additional cost
Since omega-3 fatty acids are relatively safe and the NNT in the general population is low, it may be worth supplementing all pregnant women, even without a commercially available blood test for EPA or DHA. Nevertheless, some women may find it challenging to take up to four additional pills per day for 13 or more weeks. Also, there is an associated cost with these supplements, although it is low.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018;67[2]: 100-102).
A 24-year-old G2P1 at 24 weeks’ gestation presents to your clinic for a routine prenatal visit. Her older daughter has asthma, and she wants to know if there is anything she can do to reduce her second child’s risk for it. What do you recommend?
Asthma is the most common chronic disease in children in resource-rich countries such as the United States.2 According to the CDC, 8.4% of children were diagnosed with asthma in 2015.3
Omega-3 fatty acids, found naturally in fish oil, are thought to confer anti-inflammatory properties that offer protection against asthma. Clinical trials have shown that fish oil supplementation in pregnancy results in higher levels of omega-3 fatty acids, along with anti-inflammatory changes, in offspring.4 Previous epidemiologic studies have also found that consumption of omega-3 fatty acids decreases the risk for atopy and asthma in offspring.5,6
A Cochrane review published in 2015, however, concluded that omega-3 supplementation during pregnancy had no benefit on wheeze or asthma in offspring.7 Five RCTs were included in the analysis. The largest trial, by Palmer et al, which included 706 women, showed no benefit for supplementation.8 The second largest, by Olsen et al, which included 533 women, did show a benefit (hazard ratio [HR], 0.37; number needed to treat [NNT], 19.6).9
These results, however, were limited by heterogeneity in the amount of fish oil supplemented and duration of follow-up. For example, the children in the Palmer study were followed only until age 3, which is around the time that asthma can be formally diagnosed—potentially leading to underreporting.8 In addition, the diagnosis of asthma was based on parent report of three episodes of wheezing, use of daily asthma medication, or use of a national registry—all of which can underestimate the incidence of asthma. The reported rate of childhood asthma with IgE-sensitization (rate without sensitization was not reported) was 1.8% in both study groups—much lower than the CDC’s rate of 8.4%, suggesting underdiagnosis.3,8 Due to these biases and other potential confounders, no firm conclusions can be drawn from the Cochrane review.
STUDY SUMMARY
Maternal fish oil supplementation reduces asthma in children
This single-center, double-blind RCT of 736 pregnant women evaluated the effect of 2.4 g/d of n-3 long-chain polyunsaturated fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) or placebo (olive oil), starting at an estimated gestational age of 24 to 26 weeks, on wheeze or asthma incidence in their offspring.1
Eligible women were between 22 and 26 weeks’ pregnant at the time of recruitment. Exclusion criteria included supplementation of 600 IU/d or more of vitamin D, or having any endocrine, cardiac, or renal disorders. The investigators randomized the women in a 1:1 ratio to either fish oil or placebo. Maternal EPA and DHA blood levels were tested at the time of randomization and one week after birth.
The primary outcome was persistent wheeze or asthma (after age 3, persistent wheeze was termed asthma), determined based on daily diary recordings of five episodes of troublesome lung symptoms within the past six months (each lasting for at least three consecutive days); rescue use of inhaled ß2-agonists; and/or relapse after a three-month course of inhaled glucocorticoids. Secondary outcomes included reduced incidence of respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization.
In total, 695 offspring were included in the study, with 95.5% follow-up at three years and 93.1% at five. The children had scheduled pediatric visits at 1 week; at one, three, six, 12, 18, 24, 30, and 36 months; and at 4 and 5 years. They also had acute visits for any pulmonary, allergic, or dermatologic symptoms that arose.
Results. The investigators found that the children of mothers who took fish oil had a lower risk for persistent wheeze or asthma at ages 3 to 5, compared to those who received placebo (16.9% vs 23.7%; HR, 0.69; NNT, 14.7). But this effect was significant only in the children whose mothers had baseline EPA and DHA levels in the lowest third (17.5% vs 34.1%; HR, 0.46; NNT, 5.6). Similarly, fish oil supplementation had a greater benefit in children whose mothers had consumed the least EPA and DHA before the start of the study (18.5% vs 32.4%; HR, 0.55; NNT, 7.2).
As for the secondary outcomes, only a reduction in lower respiratory infections was associated with fish oil supplementation compared with placebo (38.8% vs 45.5%; HR, 0.77; NNT, 14.9). There was no reduction in asthma exacerbations, eczema, or risk for sensitization in the fish oil group.
WHAT’S NEW?
Study adds fuel to the fire
This study strengthens the case for fish oil supplementation during pregnancy to reduce the risk for asthma in offspring, despite the recent Cochrane review that showed no benefit.1,7 The Palmer study used a much lower amount of omega-3s (900 mg/d fish oil vs 2,400 mg/d in the current trial).1,8 Olsen et al supplemented with a greater amount of omega-3s (2,700 mg/d) and did find a benefit.9 The NNT from the Olsen study (19.6) is consistent with that of the current investigation, suggesting that a higher dosage may be necessary to prevent the onset of asthma.
Additionally, this study followed children for a longer period than did the Palmer study, which may have led to more accurate diagnoses of asthma.1,8 Lastly, the diagnosis of asthma in the Palmer study was based on parent survey data and use of daily asthma medicine rather than on daily diary cards, which are often more accurate.
Consider fish consumption. Both this study and the Olsen trial were performed in Denmark.1,9 While Denmark and the United States have had a relatively similar level of fish consumption since the 1990s, women in Denmark may eat a higher proportion of oily fish than women in the United States, given the more common inclusion of mackerel and herring in their diet.10 Thus, the effect of supplementation may be more pronounced in women in the US.
CAVEATS
Ideal dose? Which women to treat?
The FDA currently recommends 8 to 12 oz of fish per week for pregnant women, but there are no guidelines on the ideal amount of fish oil to be consumed.11 The Palmer study, using 900 mg/d of fish oil, did not show a benefit, whereas there did appear to be a benefit in this study (2,400 mg/d) and the Olsen study (2,700 mg/d).1,8,9 Further research is needed to determine the optimal dosage.
The decreased risk for persistent wheeze or asthma was seen only in the children of women whose EPA and DHA blood levels were in the lowest third of the study population. Thus, only women whose blood levels are low to begin with will likely benefit from this intervention. Currently, EPA and DHA levels are not routinely checked, but there may be some benefit to doing so.
One proxy for blood levels is maternal intake of fish at baseline. The investigators found that there was an association between dietary intake of fish and blood levels of EPA and DHA (r, 0.32).1 Therefore, additional screening questions to gauge fish consumption would be useful to identify women most likely to benefit from supplementation.
CHALLENGES TO IMPLEMENTATION
Multiple pills, additional cost
Since omega-3 fatty acids are relatively safe and the NNT in the general population is low, it may be worth supplementing all pregnant women, even without a commercially available blood test for EPA or DHA. Nevertheless, some women may find it challenging to take up to four additional pills per day for 13 or more weeks. Also, there is an associated cost with these supplements, although it is low.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018;67[2]: 100-102).
1. Bisgaard H, Stokholm J, Chawes BL, et al. Fish oil-derived fatty acids in pregnancy and wheeze and asthma in offspring. N Engl J Med. 2016;375(26):2530-2539.
2. Masoli M, Fabian D, Holt S, et al. The global burden of asthma: executive summary of the GINA Dissemination Committee Report. Allergy. 2004;59(5):469-478.
3. CDC . Asthma. www.cdc.gov/asthma/most_recent_data.htm. Accessed February 1, 2018.
4. Miyata J, Arita M. Role of omega-3 fatty acids and their metabolites in asthma and allergic diseases. Allergol Int. 2015;64(1):27-34.
5. Salam MT, Li YF, Langholz B, et al. Maternal fish consumption during pregnancy and risk of early childhood asthma. J Asthma. 2005;42(6):513-518.
6. Calvani M, Alessandri C, Sopo SM, et al. Consumption of fish, butter and margarine during pregnancy and development of allergic sensitizations in the offspring: role of maternal atopy. Pediatr Allergy Immunol. 2006;17(2):94-102.
7. Gunaratne AW, Makrides M, Collins CT. Maternal prenatal and/or postnatal n-3 long chain polyunsaturated fatty acids (LCPUFA) supplementation for preventing allergies in early childhood. Cochrane Database Syst Rev. 2015;22(7): CD010085.
8. Palmer D, Sullivan T, Gold M, et al. Randomized controlled trial of fish oil supplementation in pregnancy on childhood allergies. Allergy. 2013;68:1370-1376.
9. Olsen SF, Østerdal ML, Salvig JD, et al. Fish oil intake compared with olive oil intake in late pregnancy and asthma in the offspring: 16 y of registry-based follow-up from a randomized controlled trial. Am J Clin Nutr. 2008;88(1): 167-175.
10. Helgi Library. Fish consumption per capita by country. www.helgilibrary.com/indicators/fish-consumption-per-capita/. Accessed February 1, 2018.
11. FDA Advice About Eating Fish, From the Environmental Protection Agency and Food and Drug Administration; Revised Fish Advice; Availability. Fed Regist. 2017;82:6571-6574.
1. Bisgaard H, Stokholm J, Chawes BL, et al. Fish oil-derived fatty acids in pregnancy and wheeze and asthma in offspring. N Engl J Med. 2016;375(26):2530-2539.
2. Masoli M, Fabian D, Holt S, et al. The global burden of asthma: executive summary of the GINA Dissemination Committee Report. Allergy. 2004;59(5):469-478.
3. CDC . Asthma. www.cdc.gov/asthma/most_recent_data.htm. Accessed February 1, 2018.
4. Miyata J, Arita M. Role of omega-3 fatty acids and their metabolites in asthma and allergic diseases. Allergol Int. 2015;64(1):27-34.
5. Salam MT, Li YF, Langholz B, et al. Maternal fish consumption during pregnancy and risk of early childhood asthma. J Asthma. 2005;42(6):513-518.
6. Calvani M, Alessandri C, Sopo SM, et al. Consumption of fish, butter and margarine during pregnancy and development of allergic sensitizations in the offspring: role of maternal atopy. Pediatr Allergy Immunol. 2006;17(2):94-102.
7. Gunaratne AW, Makrides M, Collins CT. Maternal prenatal and/or postnatal n-3 long chain polyunsaturated fatty acids (LCPUFA) supplementation for preventing allergies in early childhood. Cochrane Database Syst Rev. 2015;22(7): CD010085.
8. Palmer D, Sullivan T, Gold M, et al. Randomized controlled trial of fish oil supplementation in pregnancy on childhood allergies. Allergy. 2013;68:1370-1376.
9. Olsen SF, Østerdal ML, Salvig JD, et al. Fish oil intake compared with olive oil intake in late pregnancy and asthma in the offspring: 16 y of registry-based follow-up from a randomized controlled trial. Am J Clin Nutr. 2008;88(1): 167-175.
10. Helgi Library. Fish consumption per capita by country. www.helgilibrary.com/indicators/fish-consumption-per-capita/. Accessed February 1, 2018.
11. FDA Advice About Eating Fish, From the Environmental Protection Agency and Food and Drug Administration; Revised Fish Advice; Availability. Fed Regist. 2017;82:6571-6574.
Minor differences with electric and manual aspiration of molar pregnancy
Manual vacuum aspiration of molar pregnancy achieves similar outcomes to electric vacuum aspiration, although it may lead to a lower incidence of uterine synechia, according to a paper published in the April edition of Obstetrics & Gynecology.
While electric vacuum aspiration of molar pregnancy is the dominant technique in North America, in other parts of the world, such as Brazil, manual vacuum aspiration is far more commonly used.
In a retrospective cohort study, researchers looked at outcomes for 1,727 patients with molar pregnancy; 1,206 of these patients underwent electric vacuum aspiration, and 521 underwent manual vacuum aspiration.
Patients who underwent electric vacuum aspiration had significantly shorter operative times (25.3 minutes vs. 34.2 minutes; P less than .001) and showed a greater drop in hemoglobin levels after evacuation (–0.3 g/dL vs. –0.19 g/dL; P less than .001), compared with those who underwent manual vacuum aspiration.
The electric procedure was also associated with a significantly higher risk of intrauterine adhesions after the procedure, compared with the manual vacuum aspiration (5.2% vs. 1.2%; P less than .001).
Lilian Padrón, MD, of the Trophoblastic Disease Center at the Rio de Janeiro Federal University and coauthors commented that the vacuum pressure is about 100 mm Hg higher in the electric technique than it is in the manual technique, which may be responsible for the greater risk of synechia.
However, there were no significant differences seen between the two groups in the risk of developing postmolar gestational trophoblastic neoplasia (14.2% with electric vs. 17.3% with manual; P = .074) nor in the presence of metastatic disease (19.9% vs. 17.8%; P = .082) or the need for multiagent chemotherapy.
Around 13% of patients had incomplete uterine evacuation, but the risk was similar between electric and manual vacuum aspiration.
“In our sample, formed exclusively by patients with molar pregnancy, the rate of complete uterine emptying did not reach 90% with either technique,” the authors wrote. “This may reflect not only the greater amount of molar trophoblastic tissue, compared with an abortion, but also the invasiveness of molar trophoblastic cells into the maternal decidua.”
There were nine cases of uterine perforation in the electric vacuum aspiration group (0.7%), and none in the manual group, although the difference was not statistically significant.
“Although differences in rates of uterine perforation as well as prolonged length of stay were not statistically different between the groups,” the authors wrote, “both of these were rare events, and we lacked sufficient power to detect differences in rare outcomes.”
No conflicts of interest were declared.
SOURCE: Padrón L et al. Obstet Gynecol. 2018;131:652-9.
Manual vacuum aspiration of molar pregnancy achieves similar outcomes to electric vacuum aspiration, although it may lead to a lower incidence of uterine synechia, according to a paper published in the April edition of Obstetrics & Gynecology.
While electric vacuum aspiration of molar pregnancy is the dominant technique in North America, in other parts of the world, such as Brazil, manual vacuum aspiration is far more commonly used.
In a retrospective cohort study, researchers looked at outcomes for 1,727 patients with molar pregnancy; 1,206 of these patients underwent electric vacuum aspiration, and 521 underwent manual vacuum aspiration.
Patients who underwent electric vacuum aspiration had significantly shorter operative times (25.3 minutes vs. 34.2 minutes; P less than .001) and showed a greater drop in hemoglobin levels after evacuation (–0.3 g/dL vs. –0.19 g/dL; P less than .001), compared with those who underwent manual vacuum aspiration.
The electric procedure was also associated with a significantly higher risk of intrauterine adhesions after the procedure, compared with the manual vacuum aspiration (5.2% vs. 1.2%; P less than .001).
Lilian Padrón, MD, of the Trophoblastic Disease Center at the Rio de Janeiro Federal University and coauthors commented that the vacuum pressure is about 100 mm Hg higher in the electric technique than it is in the manual technique, which may be responsible for the greater risk of synechia.
However, there were no significant differences seen between the two groups in the risk of developing postmolar gestational trophoblastic neoplasia (14.2% with electric vs. 17.3% with manual; P = .074) nor in the presence of metastatic disease (19.9% vs. 17.8%; P = .082) or the need for multiagent chemotherapy.
Around 13% of patients had incomplete uterine evacuation, but the risk was similar between electric and manual vacuum aspiration.
“In our sample, formed exclusively by patients with molar pregnancy, the rate of complete uterine emptying did not reach 90% with either technique,” the authors wrote. “This may reflect not only the greater amount of molar trophoblastic tissue, compared with an abortion, but also the invasiveness of molar trophoblastic cells into the maternal decidua.”
There were nine cases of uterine perforation in the electric vacuum aspiration group (0.7%), and none in the manual group, although the difference was not statistically significant.
“Although differences in rates of uterine perforation as well as prolonged length of stay were not statistically different between the groups,” the authors wrote, “both of these were rare events, and we lacked sufficient power to detect differences in rare outcomes.”
No conflicts of interest were declared.
SOURCE: Padrón L et al. Obstet Gynecol. 2018;131:652-9.
Manual vacuum aspiration of molar pregnancy achieves similar outcomes to electric vacuum aspiration, although it may lead to a lower incidence of uterine synechia, according to a paper published in the April edition of Obstetrics & Gynecology.
While electric vacuum aspiration of molar pregnancy is the dominant technique in North America, in other parts of the world, such as Brazil, manual vacuum aspiration is far more commonly used.
In a retrospective cohort study, researchers looked at outcomes for 1,727 patients with molar pregnancy; 1,206 of these patients underwent electric vacuum aspiration, and 521 underwent manual vacuum aspiration.
Patients who underwent electric vacuum aspiration had significantly shorter operative times (25.3 minutes vs. 34.2 minutes; P less than .001) and showed a greater drop in hemoglobin levels after evacuation (–0.3 g/dL vs. –0.19 g/dL; P less than .001), compared with those who underwent manual vacuum aspiration.
The electric procedure was also associated with a significantly higher risk of intrauterine adhesions after the procedure, compared with the manual vacuum aspiration (5.2% vs. 1.2%; P less than .001).
Lilian Padrón, MD, of the Trophoblastic Disease Center at the Rio de Janeiro Federal University and coauthors commented that the vacuum pressure is about 100 mm Hg higher in the electric technique than it is in the manual technique, which may be responsible for the greater risk of synechia.
However, there were no significant differences seen between the two groups in the risk of developing postmolar gestational trophoblastic neoplasia (14.2% with electric vs. 17.3% with manual; P = .074) nor in the presence of metastatic disease (19.9% vs. 17.8%; P = .082) or the need for multiagent chemotherapy.
Around 13% of patients had incomplete uterine evacuation, but the risk was similar between electric and manual vacuum aspiration.
“In our sample, formed exclusively by patients with molar pregnancy, the rate of complete uterine emptying did not reach 90% with either technique,” the authors wrote. “This may reflect not only the greater amount of molar trophoblastic tissue, compared with an abortion, but also the invasiveness of molar trophoblastic cells into the maternal decidua.”
There were nine cases of uterine perforation in the electric vacuum aspiration group (0.7%), and none in the manual group, although the difference was not statistically significant.
“Although differences in rates of uterine perforation as well as prolonged length of stay were not statistically different between the groups,” the authors wrote, “both of these were rare events, and we lacked sufficient power to detect differences in rare outcomes.”
No conflicts of interest were declared.
SOURCE: Padrón L et al. Obstet Gynecol. 2018;131:652-9.
FROM OBSTETRICS & GYNECOLOGY
Key clinical point: Manual vacuum aspiration of molar pregnancy achieves similar outcomes to electric vacuum aspiration, although it may lead to a lower incidence of uterine synechia.
Major finding: Electric vacuum aspiration of molar pregnancy is associated with a higher risk of synechia than manual vacuum aspiration.
Data source: A retrospective cohort study in 1,727 patients with molar pregnancy.
Disclosures: No conflicts of interest were declared.
Source: Padrón L et al. Obstet Gynecol. 2018;131:652-9.
Does immediate postpartum LNG-IUD insertion negatively affect breastfeeding outcomes?
WHAT DOES THIS MEAN FOR PRACTICE?
- Immediate postpartum placement of an LNG-IUD does not negatively affect breastfeeding
- Immediate postpartum placement of an LNG-IUD may be a reasonable and appropriate option for patient populations that are not compliant with postpartum visits or for patients at high risk for short-interval pregnancies
Toxicology reveals worse maternal and fetal outcomes with teen marijuana use
DALLAS – . Also, hypertensive disorders of pregnancy were higher in marijuana users, according to a study that incorporated universal urine toxicology testing of adolescents.
The study compared maternal and fetal/neonatal outcomes in 211 marijuana-exposed with 995 unexposed pregnancies. Christina Rodriguez, MD, and her coinvestigators found that the risk of a composite adverse pregnancy outcome was higher in marijuana users, occurring in 97/211 marijuana users (46%), and in 337/995 (33.9%) of the non–marijuana users (P less than .001).
Dr. Rodriguez said that since it used biological samples to confirm marijuana exposure, the study helps fill a gap in the literature. She presented the retrospective cohort study at the meeting sponsored by the Society for Maternal-Fetal Medicine.
Previous work, she said, had established that up to 70% of pregnant women who had positive tests for tetrahydrocannabinol also denied marijuana use. “If marijuana use is determined by self-report, some women are misclassified as nonusers,” making it difficult to ascertain the true association between marijuana use during pregnancy and pregnancy outcomes, said Dr. Rodriguez of the University of Colorado, Denver.
Whether marijuana is associated with adverse pregnancy outcomes is an increasingly pressing question given rapidly shifting legislation, said Dr. Rodriguez. “In a state with legal access to marijuana, use is common in adolescent pregnancies,” she said.
Participants who were enrolled in prenatal care through the University of Colorado’s adolescent maternity program, where Dr. Rodriguez is a fellow, and who delivered at the University of Colorado Hospital, Aurora, were eligible to participate; adolescents were excluded for multiple gestation and for known major fetal anomalies or aneuploidy.
In addition to urine toxicology testing, participants also completed a uniformly administered substance use questionnaire. Marijuana exposure was defined as either having a positive urine toxicology result or self-reported marijuana use on the questionnaire (or both). Of the marijuana-exposed pregnancies, 133 (63%) of the adolescents tested positive on urine toxicology, 18 (9%) were positive by self-report, and 60 (28%) had both positive marijuana urine toxicology and positive self-report. Toxicology was available for 91% of participants.
Participants were negative for marijuana exposure if they had a negative toxicology screen, regardless of their response on the substance-use questionnaire.
The study’s primary outcome was a composite of adverse pregnancy outcomes, including stillbirth, defined as Apgar score of 0; any hypertensive disorder of pregnancy, including gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count); preterm birth, defined as spontaneous delivery before 37 weeks gestation; and infants born small for gestational age, defined as a birth weight below the 10th percentile after adjustment for gestational age and sex.
Secondary outcomes included pregnancy outcomes including placental abruption, mode of delivery, and gestational age at delivery. Neonatal outcomes included weight, length, and head circumference at birth, and neonatal intensive care unit admission. An Apgar score less than 7 at 5 minutes was considered an adverse neonatal outcome.
The sample size was determined by an estimate drawn from previous chart abstraction that the composite outcome would be seen in 16% of the clinic’s non–marijuana exposed patients, and 24% of the marijuana-exposed patients. The investigators also factored in that 18% of adolescents in the clinic database were marijuana users.
Dr. Rodriguez and her collaborators used a variety of models for statistical analysis, some of which included self-report alone or in conjunction with urine toxicology. In the end, they found that significant associations between their composite endpoint and marijuana use were seen when patients were dichotomized into those who had at least one positive urine toxicology test, versus those who had no positive toxicology results.
One of the study limitations was that the study didn’t permit investigators to get accurate information about the quantity, timing, or route of marijuana dosing. Also, this methodology may primarily identify heavier marijuana users, said Dr. Rodriguez.
Tobacco use was determined only by self-report, and outcomes were followed over a relatively short period of time.
Still, said Dr. Rodriguez, the study had many strengths, including the use of biological sampling to determine exposure and the near-universal participant urine toxicology testing. The investigators were able to capture and account for many important factors that could confound the results, she said. “Uncertainty regarding the impact of [marijuana] on pregnancy outcomes in the literature may result from incomplete ascertainment of exposure,” she and her coinvestigators wrote in the abstract accompanying the presentation.
SOURCE: Rodriguez C et al. Am J Obstet Gynecol. 2018 Jan;218:S37.
DALLAS – . Also, hypertensive disorders of pregnancy were higher in marijuana users, according to a study that incorporated universal urine toxicology testing of adolescents.
The study compared maternal and fetal/neonatal outcomes in 211 marijuana-exposed with 995 unexposed pregnancies. Christina Rodriguez, MD, and her coinvestigators found that the risk of a composite adverse pregnancy outcome was higher in marijuana users, occurring in 97/211 marijuana users (46%), and in 337/995 (33.9%) of the non–marijuana users (P less than .001).
Dr. Rodriguez said that since it used biological samples to confirm marijuana exposure, the study helps fill a gap in the literature. She presented the retrospective cohort study at the meeting sponsored by the Society for Maternal-Fetal Medicine.
Previous work, she said, had established that up to 70% of pregnant women who had positive tests for tetrahydrocannabinol also denied marijuana use. “If marijuana use is determined by self-report, some women are misclassified as nonusers,” making it difficult to ascertain the true association between marijuana use during pregnancy and pregnancy outcomes, said Dr. Rodriguez of the University of Colorado, Denver.
Whether marijuana is associated with adverse pregnancy outcomes is an increasingly pressing question given rapidly shifting legislation, said Dr. Rodriguez. “In a state with legal access to marijuana, use is common in adolescent pregnancies,” she said.
Participants who were enrolled in prenatal care through the University of Colorado’s adolescent maternity program, where Dr. Rodriguez is a fellow, and who delivered at the University of Colorado Hospital, Aurora, were eligible to participate; adolescents were excluded for multiple gestation and for known major fetal anomalies or aneuploidy.
In addition to urine toxicology testing, participants also completed a uniformly administered substance use questionnaire. Marijuana exposure was defined as either having a positive urine toxicology result or self-reported marijuana use on the questionnaire (or both). Of the marijuana-exposed pregnancies, 133 (63%) of the adolescents tested positive on urine toxicology, 18 (9%) were positive by self-report, and 60 (28%) had both positive marijuana urine toxicology and positive self-report. Toxicology was available for 91% of participants.
Participants were negative for marijuana exposure if they had a negative toxicology screen, regardless of their response on the substance-use questionnaire.
The study’s primary outcome was a composite of adverse pregnancy outcomes, including stillbirth, defined as Apgar score of 0; any hypertensive disorder of pregnancy, including gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count); preterm birth, defined as spontaneous delivery before 37 weeks gestation; and infants born small for gestational age, defined as a birth weight below the 10th percentile after adjustment for gestational age and sex.
Secondary outcomes included pregnancy outcomes including placental abruption, mode of delivery, and gestational age at delivery. Neonatal outcomes included weight, length, and head circumference at birth, and neonatal intensive care unit admission. An Apgar score less than 7 at 5 minutes was considered an adverse neonatal outcome.
The sample size was determined by an estimate drawn from previous chart abstraction that the composite outcome would be seen in 16% of the clinic’s non–marijuana exposed patients, and 24% of the marijuana-exposed patients. The investigators also factored in that 18% of adolescents in the clinic database were marijuana users.
Dr. Rodriguez and her collaborators used a variety of models for statistical analysis, some of which included self-report alone or in conjunction with urine toxicology. In the end, they found that significant associations between their composite endpoint and marijuana use were seen when patients were dichotomized into those who had at least one positive urine toxicology test, versus those who had no positive toxicology results.
One of the study limitations was that the study didn’t permit investigators to get accurate information about the quantity, timing, or route of marijuana dosing. Also, this methodology may primarily identify heavier marijuana users, said Dr. Rodriguez.
Tobacco use was determined only by self-report, and outcomes were followed over a relatively short period of time.
Still, said Dr. Rodriguez, the study had many strengths, including the use of biological sampling to determine exposure and the near-universal participant urine toxicology testing. The investigators were able to capture and account for many important factors that could confound the results, she said. “Uncertainty regarding the impact of [marijuana] on pregnancy outcomes in the literature may result from incomplete ascertainment of exposure,” she and her coinvestigators wrote in the abstract accompanying the presentation.
SOURCE: Rodriguez C et al. Am J Obstet Gynecol. 2018 Jan;218:S37.
DALLAS – . Also, hypertensive disorders of pregnancy were higher in marijuana users, according to a study that incorporated universal urine toxicology testing of adolescents.
The study compared maternal and fetal/neonatal outcomes in 211 marijuana-exposed with 995 unexposed pregnancies. Christina Rodriguez, MD, and her coinvestigators found that the risk of a composite adverse pregnancy outcome was higher in marijuana users, occurring in 97/211 marijuana users (46%), and in 337/995 (33.9%) of the non–marijuana users (P less than .001).
Dr. Rodriguez said that since it used biological samples to confirm marijuana exposure, the study helps fill a gap in the literature. She presented the retrospective cohort study at the meeting sponsored by the Society for Maternal-Fetal Medicine.
Previous work, she said, had established that up to 70% of pregnant women who had positive tests for tetrahydrocannabinol also denied marijuana use. “If marijuana use is determined by self-report, some women are misclassified as nonusers,” making it difficult to ascertain the true association between marijuana use during pregnancy and pregnancy outcomes, said Dr. Rodriguez of the University of Colorado, Denver.
Whether marijuana is associated with adverse pregnancy outcomes is an increasingly pressing question given rapidly shifting legislation, said Dr. Rodriguez. “In a state with legal access to marijuana, use is common in adolescent pregnancies,” she said.
Participants who were enrolled in prenatal care through the University of Colorado’s adolescent maternity program, where Dr. Rodriguez is a fellow, and who delivered at the University of Colorado Hospital, Aurora, were eligible to participate; adolescents were excluded for multiple gestation and for known major fetal anomalies or aneuploidy.
In addition to urine toxicology testing, participants also completed a uniformly administered substance use questionnaire. Marijuana exposure was defined as either having a positive urine toxicology result or self-reported marijuana use on the questionnaire (or both). Of the marijuana-exposed pregnancies, 133 (63%) of the adolescents tested positive on urine toxicology, 18 (9%) were positive by self-report, and 60 (28%) had both positive marijuana urine toxicology and positive self-report. Toxicology was available for 91% of participants.
Participants were negative for marijuana exposure if they had a negative toxicology screen, regardless of their response on the substance-use questionnaire.
The study’s primary outcome was a composite of adverse pregnancy outcomes, including stillbirth, defined as Apgar score of 0; any hypertensive disorder of pregnancy, including gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count); preterm birth, defined as spontaneous delivery before 37 weeks gestation; and infants born small for gestational age, defined as a birth weight below the 10th percentile after adjustment for gestational age and sex.
Secondary outcomes included pregnancy outcomes including placental abruption, mode of delivery, and gestational age at delivery. Neonatal outcomes included weight, length, and head circumference at birth, and neonatal intensive care unit admission. An Apgar score less than 7 at 5 minutes was considered an adverse neonatal outcome.
The sample size was determined by an estimate drawn from previous chart abstraction that the composite outcome would be seen in 16% of the clinic’s non–marijuana exposed patients, and 24% of the marijuana-exposed patients. The investigators also factored in that 18% of adolescents in the clinic database were marijuana users.
Dr. Rodriguez and her collaborators used a variety of models for statistical analysis, some of which included self-report alone or in conjunction with urine toxicology. In the end, they found that significant associations between their composite endpoint and marijuana use were seen when patients were dichotomized into those who had at least one positive urine toxicology test, versus those who had no positive toxicology results.
One of the study limitations was that the study didn’t permit investigators to get accurate information about the quantity, timing, or route of marijuana dosing. Also, this methodology may primarily identify heavier marijuana users, said Dr. Rodriguez.
Tobacco use was determined only by self-report, and outcomes were followed over a relatively short period of time.
Still, said Dr. Rodriguez, the study had many strengths, including the use of biological sampling to determine exposure and the near-universal participant urine toxicology testing. The investigators were able to capture and account for many important factors that could confound the results, she said. “Uncertainty regarding the impact of [marijuana] on pregnancy outcomes in the literature may result from incomplete ascertainment of exposure,” she and her coinvestigators wrote in the abstract accompanying the presentation.
SOURCE: Rodriguez C et al. Am J Obstet Gynecol. 2018 Jan;218:S37.
REPORTING FROM THE PREGNANCY MEETING
Key clinical point: Maternal and fetal outcomes were worse when marijuana use was detected by urine toxicology.
Major finding: A composite adverse outcome occurred in 46% of adolescent marijuana users, compared with 34% of non–marijuana users (P less than .001).
Study details: Retrospective cohort study of participants in an adolescent maternity clinic.
Disclosures: The authors reported no conflicts of interest.
Source: Rodriguez C et al. Am J Obstet Gynecol. 2018 Jan;218:S37.