Pregnant Women Raise Risk of Complications by Using OTC Pain Relievers

By Pat Anson, PNN Editor

Pregnant women who take over-the-counter pain relievers are one-and-a-half times more likely to have complications, including stillbirth and premature delivery, according to a large new study.

Researchers at the University of Aberdeen analyzed data from over 151,000 pregnancies in the UK from 1985-2015, looking for medical notes indicating the women used paracetamol (acetaminophen), aspirin or the non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac, naproxen and ibuprofen — either alone or in combinations.

The findings, recently published in BMJ Open, show a significantly higher risk of a preterm delivery, neonatal death, low birth weight and other health problems in babies born to mothers who used OTC pain relievers. Neural tube defects of the brain, spine or spinal cord were 64% more likely; while hypospadias, a birth defect affecting the penis, was 27% more likely.

“Over-the-counter analgesics consumption during pregnancy was associated with a substantially higher risk for adverse perinatal health outcomes in the offspring. The use of paracetamol in combination with other non-steroidal anti-inflammatory drugs conferred the highest risk,” wrote lead author Aikaterini Zafeiri, PhD. “The increased risks of adverse neonatal outcomes associated with non-prescribed, over-the-counter, analgesics use during pregnancy indicate that healthcare guidance for pregnant women regarding analgesic use need urgent updating.”

One of the more surprising aspects of the study is how use of the five analgesics by pregnant women grew dramatically over the 30-year study period.  In 1985, only 1.8% reported using one of the pain relievers. By 2015, that had grown to 70.6% -- with most of the increase coming in the last seven years of the study.

Although it is believed to be one of the largest and most comprehensive studies of its kind, the research was limited. The duration, dose and stage of the pregnancy when analgesics were consumed were not recorded. The health of the mothers and babies later in life was also not studied.

But given the substantial increase in analgesic use during pregnancy and the higher risk of complications, researchers say more caution is needed on use of the drugs.

“The ease of access to non-prescription painkillers, in combination with availability of misinformation as well as correct information through the internet, raises safety concerns,” said Zafeiri. “It should be reinforced that paracetamol in combination with NSAIDs is associated with a higher risk and pregnant women should always consult their doctor or midwife before taking any over-the-counter drugs. We would encourage a strong reinforcement of the official advice for pregnant women.”   

Previous studies have linked prenatal use of paracetamol to autism, hyperactivity and behavioral problem in children. Despite the findings, drug regulators in the UK and US maintain that it is safe for pregnant women to use paracetamol (acetaminophen).

“Paracetamol is the first choice of painkiller if you're pregnant or breastfeeding. It's been taken by many pregnant and breastfeeding women with no harmful effects in the mother or baby,” the UK’s National Health Service (NHS) says on its website.

The Food and Drug Administration also does not caution pregnant women about using acetaminophen. The agency said in 2015 that the evidence was “too limited” to justify such a warning.  

Meanwhile, drug regulators in Australia are so concerned about recent deaths involving paracetamol that they may restrict access to the drug. Australia’s Therapeutic Goods Administration (TGA) has commissioned a report by an expert panel on the risks of paracetamol misuse.

“While paracetamol has well established safety and toxicity profiles, the wide use is paralleled by a high prevalence of accidental and deliberate paracetamol poisoning in the community, in both adults and children,” the TGA said in a statement earlier this month.

“The TGA is aware of concerns, particularly of families and healthcare professionals of affected consumers of paracetamol, regarding the number of poisonings and deliberate overdoses from paracetamol obtained from general retail outlets, and whether current access restrictions are appropriate.”

Australia currently regulates the quantity and dose of paracetamol sold over-the-counter. The independent commission will consider if stricter buying limits should be imposed. 

UK Warns Pregnant Women About Taking Pregabalin

By Pat Anson, PNN Editor

Health officials in the UK are warning women of childbearing age that pregabalin (Lyrica), a drug commonly prescribed for pain, anxiety and epilepsy, raises the risk of major birth defects.

A recent study in four Nordic countries of over 2,700 pregnancies found that 5.6% of babies born to women who took pregabalin in the first three months of pregnancy had birth abnormalities. That compares to 4.1% of babies whose mothers did not use pregabalin.  

“The study showed that taking pregabalin during early pregnancy was associated with a slightly increased chance of having a baby who is born with a physical birth abnormality. It is important to note that this study could not show that pregabalin was the cause of the physical birth abnormalities,” the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) said in a new safety alert.

The birth defects associated with pregabalin primarily involved the nervous system, eyes, face, urinary system and genitals. The MHRA – which regulates drugs in the UK – cautioned pregnant women not to stop taking pregabalin without talking to a doctor first.

“If you think you may be pregnant and are currently taking pregabalin, you should set up an appointment with your GP, specialist or nurse at your earliest opportunity, to discuss any concerns you may have. However, do continue to take pregabalin as prescribed until you can speak to them,” the MHRA alert said. “Untreated epilepsy, pain, or anxiety could be harmful to you and your unborn baby. It is important that you talk to your healthcare professional before stopping pregabalin or making any changes to your usual medicines.”

An international study in 2016 also linked pregabalin to birth defects. Women taking pregabalin were found to be six times more likely to have a baby with a major birth defect, including abnormalities in the heart, central nervous system (CNS) and other organs.

Pregabalin Concerns

In recent years, pregabalin has come under increased scrutiny in the UK.  In 2021, the MHRA said pregabalin was associated with serious breathing problems in people over age 65 and in patients with compromised respiratory systems.

Doctors in Northern Ireland were also told last year not to prescribe pregabalin for neuropathic pain due to a “significant increase” in drug-related deaths involving the drug.

In 2019, pregabalin and gabapentin (Neurontin) were both rescheduled as Class C drugs in the UK due to a rising number of overdose deaths. Health experts said the medications cause “an elevated mood in users” and could have serious side effects when combined with other drugs.

Lyrica and Neurontin are two of Pfizer’s top selling drugs and generate billions of dollars in annual sales. They belong to a class of nerve medication called gabapentinoids that were originally developed to treat seizures, but are now widely prescribed as an alternative to opioid painkillers. A 2019 study found little evidence that gabapentinoids should be used to treat pain and said their effectiveness was often exaggerated by prescribing guidelines.

In the United States, where Lyrica is approved for fibromyalgia, neuropathic pain, seizures and postherpetic neuralgia, the FDA’s lengthy warning label states that “there are no adequate and well-controlled studies with Lyrica in pregnant women,” but at the same time cautions that “Lyrica may harm your unborn baby.”  

An earlier warning label said it was “not known if Lyrica will harm your unborn baby.”

Acetaminophen Use by Pregnant Women Raises Risk of Autism or ADHD in Children

By Pat Anson, PNN Editor 

A large new study in Europe is adding to the growing body of evidence that the use acetaminophen (paracetamol) by pregnant women raises the risk of their children having autism or Attention-Deficit Hyperactivity Disorder (ADHD)

Researchers at the University of Barcelona followed nearly 74,000 mothers and their children in the UK and five other European countries, finding that women who took the pain reliever while pregnant were 19% more likely to have children with Autism Spectrum Conditions (ASC) and 21% more likely to develop ADHD symptoms.

“Associations between prenatal acetaminophen and ASC and ADHD symptoms were consistently positive for both boys and girls albeit slightly stronger among boys,” researchers reported in the European Journal of Epidemiology.

Several previous studies have linked prenatal use of acetaminophen to autism, ADHD and hyperactivity in children, but this was by far the largest. Although the exact cause is unknown, it’s believed acetaminophen affects a baby’s brain development and growth, especially during the third trimester. The study found no evidence that acetaminophen raised the risk of autism and ADHD after the children were born.

Despite the findings, the UK’s National Health Service (NHS) maintains that it is safe for pregnant women to use paracetamol.

“Paracetamol is the first choice of painkiller if you're pregnant or breastfeeding. It's been taken by many pregnant and breastfeeding women with no harmful effects in the mother or baby,” the NHS says on its website.

The U.S. Food and Drug Administration also does not caution pregnant women about using acetaminophen. The agency said in 2015 that the evidence was “too limited” to justify such a warning.  

The University of Barcelona researchers are a bit more cautious, saying pregnant women should take acetaminophen “only when necessary.”

“Considering all evidences on acetaminophen use and neurodevelopment, we agree with previous recommendations indicating that while acetaminophen should not be suppressed in pregnant women or children, it should be used only when necessary,” they said.

Acetaminophen is the most popular pain reliever in the world, and is used by over half the pregnant women in Europe and the United States. It is the active ingredient in Tylenol, Excedrin, and hundreds of pain medications. Excessive use of acetaminophen can cause liver, kidney, heart and blood pressure problems. A recent study found little or no evidence to support its use for most pain conditions.  

Criminalizing Pregnant Women for Drug Abuse Is a Terrible Idea

By Dr. Lynn Webster, PNN Columnist

According to Guttmacher Institute, nearly half the states in the United States are willing to punish pregnant women in order to spare their babies the agony of being born with Neonatal Abstinence Syndrome (NAS). Ironically, their efforts are having the opposite effect.

Twenty-three states and the District of Columbia have passed legislation that criminalizes substance abuse during pregnancy. Additionally, 25 states and the District of Columbia require healthcare providers to report expectant mothers who may be illegally using substances. In 8 states, pregnant women who are suspected of substance abuse must also undergo drug testing.

The huge number of babies born to mothers dependent on opioids has driven policymakers to find ways to deter pregnant women from abusing opioids.

But new research points out there are unintended consequences to criminalization. And it provides lawmakers insight on how to create more effective policies that result in positive, not punitive, outcomes.

A study published recently in the journal JAMA Network Open examined 4.6 million births in the U.S. from 2000 to 2014. During this time, the diagnosis of NAS increased seven fold.

The study was conducted by the RAND Corporation, a nonprofit research institute that analyzed 8 states with punitive policies for drug-abusing pregnant women. The research was funded by the National Institute of Drug Abuse.

According to a RAND press release, Arkansas, Arizona, Colorado, Kentucky, Massachusetts, Maryland, Nevada and Utah adopted either punitive penalties for drug use during pregnancy or policies that required health care providers to report pregnant women with suspected illegal substance use.

RAND researchers found that the annual rate of NAS increased in the 8 states, from 46 cases per 10,000 live births to 60 cases per 10,000 after punitive policies were enacted. That is an alarming 30% increase in NAS cases.

This is not the first study that has shown political efforts to curb opioid addiction and overdoses have not had a positive impact. We have seen the harm associated with forced tapers and dose limits adversely affecting millions of pain patients.

It is hard to understand why these destructive policies are put in place, but it may be because policymakers are misinformed or biased. Regardless, it reflects a systemic flaw for governments to fail to evaluate the efficacy and outcomes of the very policies they create.

Addiction Is a Disease, Not a Crime

How best to address addiction has long been the subject of debate. For example, a state hospital in South Carolina illegally obtained the diagnostic tests of pregnant women in an effort “to obtain evidence of a patient's criminal conduct for law enforcement purposes” (this was the case of Ferguson v. Charleston).

Unfortunately, some people still believe that addiction is a volitional or character flaw that should be recognized as criminal behavior rather than a disease.

Indisputably, addiction is a complicated, life-threatening disease. Treating people with the disease as criminals is the worst possible approach. Most experts in the substance abuse treatment community have known this for years. Fortunately, the RAND Corporation has now provided evidence of how this applies to babies born to women who abuse opioids. 

Typically, lawmakers do not evaluate the impact of the policies they pass. There have been many policies over the past few years that were implemented by state legislatures, healthcare organizations and insurance companies that were intended to reduce harm from opioids. Almost no one has attempted to measure their effectiveness or unintended consequences.

Fortunately, in this case, we have an exception. We have a unique opportunity as a result. The RAND study should provide policymakers with insights on how to more effectively address the problem of substance abuse during pregnancy.

Threatening to punish a pregnant women does not decrease the number of women who abuse drugs. However, it does scare many of them away from seeking the treatment they need and can deter pregnant mothers from seeking prenatal care.

Pregnant women who are opioid-dependent frequently use other illegal substances that risk the health of their babies. There should not be more barriers for pregnant women to receive prenatal care. Infants born after exposure to opioids often require prolonged hospitalizations to manage their needs, with those cumulative costs totaling more than $500 million, according to the RAND study. More importantly, babies with NAS suffer needlessly.

It should go without saying that every policymaker wants to solve problems and not create additional harm for new mothers or to babies born to them. Hopefully, this study will be used as it is intended: to help create policies that actually reduce harm from opioids. 

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is the author of the award-winning book, “The Painful Truth,” and co-producer of the documentary, “It Hurts Until You Die.”

You can find Lynn on Twitter: @LynnRWebsterMD.

Opinions expressed here are those of the author alone and do not reflect the views or policy of PRA Health Sciences or Pain News Network. 

Acetaminophen Linked to Hyperactivity and Behavior Problems in Children

By Pat Anson, PNN Editor

A new study is adding to the growing body of evidence linking maternal use of acetaminophen to hyperactivity and other behavioral problems in children. Acetaminophen – which is more commonly known as paracetamol outside the U.S. – is the world’s most widely used over-the-counter pain reliever.

British researchers have been following over 14,000 children born in 1991 and 1992 who are enrolled in the Avon Longitudinal Study of Parents and Children. The children’s health, cognitive skills, temperament and behavior were regularly evaluated as they grew older.

Children with mothers who regularly used acetaminophen in mid to late pregnancy were more likely to be hyperactive, less adaptable and to have conduct problems in their pre-school years. The attention and hyperactivity issues appear to lessen by age 7, although boys exposed to the drug were more likely to have conduct problems until age 9.

“We have shown that paracetamol consumption between 18 and 32 weeks gestation was associated with adverse trends in pre‐school child behaviour, but the associations were no longer present by the end of primary school (age 10‐11 years). Boys appeared to be more susceptible than girls to possible behavioural effects of the drug,” researchers reported in the journal Paediatric and Perinatal Health.

Acetaminophen is used by over half the pregnant women in the United States and European Union. It is the active ingredient in Tylenol, Excedrin, and hundreds of pain medications.

Previous studies have linked maternal use of acetaminophen to asthma, autism and attention deficit disorder (ADHD) in children, as well as early puberty and slow language development in girls.

“Our findings add to a series of results concerning evidence of the possible adverse effects of taking paracetamol during pregnancy such as issues with asthma or behaviour in the offspring,” said lead author Professor Jean Golding of the University of Bristol.

“It reinforces the advice that women should be cautious when taking medication during pregnancy and to seek medical advice where necessary.”

Despite the findings, the UK’s National Health Service (NHS) maintains that it is “usually safe” for pregnant women to use paracetamol.

“Paracetamol has been used routinely during all stages of pregnancy to reduce a high temperature and for pain relief. There's no clear evidence it has any harmful effects on an unborn baby,” the NHS says on its website.

The FDA’s warning label for acetaminophen cautions people about the risk of liver damage and other side effects, but does not specifically warn pregnant women about using the pain reliever. The agency said in 2015 that the evidence was “too limited” to justify such a warning.  

Acetaminophen May Slow Language Development

By Pat Anson, Editor

Another study has linked acetaminophen to learning difficulties in young children born to mothers who used the over-the-counter pain reliever during pregnancy.

Researchers at the Icahn School of Medicine in New York City say toddlers exposed to acetaminophen in the womb had a slower rate of language development at 30 months. The findings are consistent with other studies reporting higher rates of autism, attention deficit disorder (ADHD) and behavioral problems in children born to mothers who used acetaminophen while pregnant.  

Acetaminophen (paracetamol) is one of the most widely used pain relievers in the world. It is the active ingredient in Tylenol, Excedrin, and hundreds of other pain medications. Researchers say over half the pregnant women in the United States and European Union use the drug.

“Given the prevalence of prenatal acetaminophen use and the importance of language development, our findings, if replicated, suggest that pregnant women should limit their use of this analgesic during pregnancy,” said senior author Shanna Swan, PhD, Professor of Environmental and Public Health at the Icahn School of Medicine at Mount Sinai.

“It’s important for us to look at language development because it has shown to be predictive of other neurodevelopmental problems in children.”

The study involved 754 women who enrolled in the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy study (SELMA) during weeks 8-13 of their pregnancy. Researchers asked the women to report the number of acetaminophen tablets they took between conception and enrollment, and tested the acetaminophen concentration in their urine.

A delay in a child's language development, defined as the use of fewer than 50 words at 30 months of age, was measured by a nurse and a follow-up questionnaire filled out by the mothers.

Girls born to mothers with high exposure -- those who took acetaminophen more than six times in early pregnancy -- were nearly six times more likely to have language delay than girls born to mothers who did not take acetaminophen.

While the number of acetaminophen tablets and concentration in urine were associated with a significant increase in language delay in girls, there was only a slight increase in boys.  The findings suggest that acetaminophen use in pregnancy results in the loss of the well-recognized female advantage in language development in early childhood.

The study is published online in the journal European Psychiatry. Researchers will follow-up with the children and re-examine their language development at age seven.

A 2016 study of over 2,600 Spanish women linked acetaminophen to autism and attention deficit problems in their children. Studies in Denmark and New Zealand have also linked acetaminophen to a higher risk of ADHD.

Over 50 million people in the U.S. use acetaminophen each week to treat pain and fever. The pain reliever has long been associated with liver injury and allergic reactions such as skin rash. In the U.S. over 50,000 emergency room visits each year are caused by acetaminophen, including 25,000 hospitalizations and 450 deaths.