NSAID Lawsuit Information - Neonatal Kidney Injuries
The NSAID lawsuits claim that the use of various pain and fever-reducer medicines during pregnancy can cause neonatal kidney injury, kidney failure, and oligohydramnios (lack of amniotic fluid).
We are no longer handling NSAID cases.
What Do We Know About NSAID Lawsuits?
On October 15, 2020, the FDA issued a Drug Safety Communication regarding an increased risk of kidney (renal) failure and oligohydramnios (insufficient amniotic fluid) in fetuses observed in association with maternal use of NSAIDs after week 20 of pregnancy. Oligohydramnios has been estimated to affect approximately 4.4% of full-term pregnancies, although rates in both directions have been reported across studies. (Hou et al., 2018).
What Are Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)?
NSAIDs include pain and fever reducers such as:
The following table lists the various generic NSAIDs and the brand names associated with each:
|Generic Name||Brand Names|
|Aspirin||Aggrenox (combination with dipyridamole), Durlaza, Equagesic (combination with meprobamate), Excedrin Migraine, Fiorinal (combination with butalbital, caffeine), Fiorinal with codeine, Lanorinal (combination with butalbital, caffeine), Norgesic (combination with caffeine, orphenadrine), Percodan (combination with oxycodone), Synalgos-DC (combination with caffeine, dihydrocodeine), Yosprala (combination with omeprazole), Vazalore|
|celecoxib||Celebrex, Consensi (combination with amlodipine), Elyxyb|
|diclofenac||Cambia, Cataflam, Dyloject, Flector, Licart, Pennsaid, Solaraze, Voltaren, Voltaren-XR, Zipsor, Zorvolex, Arthrotec (combination with misoprostol)|
|diflunisal||No brand name currently marketed|
|etodolac||No brand name currently marketed|
|flurbiprofen||No brand name currently marketed|
|ibuprofen||Advil, Advil Dual Action, Caldolor, Ibu-Tab, Ibuprohm, Midol, Motrin IB, Motrin Migraine Pain, Profen, Tab-Profen, Duexis (combination with famotidine), Reprexain (combination with hydrocodone), Sine-Aid IB (combination with pseudoephedrine), Vicoprofen (combination with hydrocodone)|
|indomethacin||Indocin, Indocin SR, Tivorbex|
|ketoprofen||No brand name currently marketed|
|meclofenamate||No brand name currently marketed|
|meloxicam||Anjeso, Mobic, Qmizz ODT, Vivlodex|
|nabumetone||No brand name currently marketed|
|naproxen||Aleve, Aleve-24, Anaprox, Anaprox DS, EC-Naprosyn, Naprelan, Naprosyn, Treximet (combination with sumatriptan), Vimovo (combination with esomeprazole)|
|oxaprozin||Daypro, Daypro Alta|
|sulindac||No brand name currently marketed|
|tolmetin||No brand name currently marketed|
Cases in the FDA’s Adverse Events Reporting System
At the time of the FDA’s October 2020 communication, the federal agency advised it had received reports of the following adverse events involving oligohydramnios or neonatal renal dysfunction associated with the use of NSAIDs during pregnancy:
- Oligohydramnios: 32 cases
- Oligohydramnios and neonatal renal dysfunction: 8 cases
- Neonatal renal dysfunction that did not report oligohydramnios: 3 cases
- Death from neonatal renal failure: 5 cases
The FDA also referenced 27 studies published between 1980 and 2016, including 17 case reports, clinical trials, and observational studies reporting on NSAID exposure and oligohydramnios, as well as 10 case reports or case series reporting on NSAID exposure and neonatal kidney failure.
Product labels for prescription NSAIDs were updated in 2020 to include the 20 week gestation warning. Prior to these labeling updates, prescription NSAID labels recommended avoiding use in pregnant women starting at 30 weeks of gestation based on the risk of premature closure of the fetal ductus arteriosus.
Product Label Update: Section 5.11 Fetal Toxicity
Premature Closure of Fetal Ductus Arteriosus
Avoid use of NSAIDs, including CELEBREX, in pregnant women at about 30 weeks gestation and later. NSAIDs, including CELEBREX, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age.
Oligohydramnios/Neonatal Renal Impairment
Use of NSAIDs, including CELEBREX, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit CELEBREX use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if CELEBREX treatment extends beyond 48 hours. Discontinue CELEBREX if oligohydramnios occurs and follow up according to clinical practice [see Use in Specific Populations (8.1)].
Additionally, the labeling for over-the-counter (OTC) NSAIDs were revised to advise that NSAIDs should not be used “20 weeks or later in pregnancy unless definitely directed to do so by a doctor because it may cause problems in the unborn child or complications during delivery.”
NSAID Injuries and Side Effects
Studies have linked NSAID use during pregnancy to several medical complications.
Neonatal Kidney Injury and Kidney Failure
Kidneys are vital organs, as they remove waste and extra fluids from the body. By filtering blood and eliminating waste and acids, kidneys maintain the balance of water, minerals, and salts in the body. Hormones produced by the kidneys aid in blood pressure control, production of red blood cells, and maintaining strong, healthy bones.
When an infant’s kidneys suddenly lose their ability to filter waste products from the blood, acute renal (kidney) failure quickly develops. According to the Mayo Clinic, this deterioration typically occurs in fewer than several days.
Outcomes of Renal Failure
Complications from acute kidney failure can include:
- Fluid building in the lungs, causing shortness of breath
- Chest pain, if the pericardium becomes inflamed
- Muscle weakness, due to an imbalance of electrolytes and body fluids
- Permanent kidney damage, also called end-stage renal disease, requiring permanent dialysis or a kidney transplant
Treatments for Renal Failure
A diagnosis of renal failure usually requires hospitalization. Physicians will attempt to treat the underlying cause of the kidney damage while trying to prevent complications. These treatments could include:
- IV fluids to restore the body’s balance of fluids
- Medications to combat high levels of potassium in the blood
- Medications/infusions to restore low calcium levels
- Dialysis to remove toxins that build up in the blood
The Merck Manual defines oligohydramnios as a “deficient volume of amniotic fluid.” The condition is associated with maternal and fetal complications and can be caused by insufficient uteroplacental, resulting from preeclampsia, chronic hypertension, thrombotic disorder, or abruptio placentae.
This medical source also attributes oligohydramnios to certain drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs).
The Importance of Amniotic Fluid
Amniotic fluid is vital to the fetus’ health. The Mayo Clinic describes the roles of this cushioning fluid as follows:
- Protecting the baby from injury
- Enabling the fetus’ growth, development, and movement
- Prevents the umbilical cord from becoming compressed between the fetus and the uterine wall
- Indicates the baby’s well-being by reflecting urine output
Outcomes of Low Amniotic Fluid
Oligohydramnios can lead to multiple complications, depending on the level of amniotic fluid present and the cause of the condition. Some of these complications include:
- Restricted growth of the uterus
- Limb contractures
- Incomplete or delayed maturation of the lung
- Cesarean delivery, due to the fetus’ inability to tolerate labor
- Fetal death
Treatments for Oligohydramnios
According to the Mayo Clinic, no long-term treatment of low amniotic fluid has proven effective. For pregnant women in their 36th to 37th week of pregnancy, delivery is sometimes the safest treatment. In earlier stages of pregnancy, a diagnosis of low amniotic fluid could require monitoring the fetus with ultrasounds. During labor, oligohydramnios could prompt an amnioinfusion, which involves placing a catheter in the cervix to deliver saline into the amniotic sac.
The Timeline Important to the NSAID Neonatal Kidney Injury, Kidney Failure, and Oligohydramnios Lawsuits
10/15/2020: The FDA issues a press release warning that “a Type of Pain and Fever Medication in Second Half of Pregnancy Could Lead to Complications”
11/3/2020: The FDA publishes a Drug Safety Communication recommending pregnant women avoid the use of NSAIDs at 20 weeks or later because such use can result in low amniotic fluid. The communication specifically indicates that NSAIDs may cause rare kidney problems in unborn babies.
11/16/2021: The FDA issues Drug Safety-related Labeling Changes (SrLC) for Motrin IB. (underlined portion is the label revisions): If pregnant or breast-feeding, ask a health professional before use. It is especially important not to use ibuprofen at 20 weeks or later in pregnancy unless definitely directed to do so by a doctor because it may cause problems in the unborn child or complications during delivery
12/14/2021: FDA issues Drug Safety-related Labeling Changes (SrLC) for Advil, as follows (underlined portion is the label revisions): If pregnant or breast-feeding, ask a health professional before use. It is especially important not to use ibuprofen at 20 weeks or later in pregnancy unless definitely directed to do so by a doctor because it may cause problems in the unborn child or complications during delivery.
3/10/2022: FDA issues Drug Safety-related Labeling Changes (SrLC) for Aleve, as follows (underlined portion is the label revisions): If pregnant or breast-feeding, ask a health professional before use. It is especially important not to use ibuprofen at 20 weeks or later in pregnancy unless definitely directed to do so by a doctor because it may cause problems in the unborn child or complications during delivery.
What Is the Purpose of NSAIDs?
NSAIDs are anti-inflammatory drugs used to relieve pain and fever. According to the Cleveland Clinic, common uses of NSAIDs include the treatment of:
- Rheumatoid arthritis, tendonitis, and osteoarthritis pain
- Muscle aches
- Gout pain
- Dental pain
- Menstrual cramps
- Aches and fever from the common cold
The drugs work by impeding the production of the inflammation-causing enzyme cyclooxygenase (COX) in the body. These medications can be purchased as either prescription or over-the-counter products. Some common brand names for prescription NSAIDs include:
Some common brand names for over-the-counter NSAIDs include:
Scientific Studies Regarding NSAID Use During Pregnancy & Neonatal Kidney Injury, Kidney Failure, and Oligohydramnios
In this research project, the authors explore the pathophysiology, etiology, evaluation, and treatment of oligohydramnios. Read more at StatPearls (2021 Sep)
Acute renal failure in the newborn
The author reviews the causes of acute renal failure in newborns, as well as the management of complications once renal failure has been established. This includes balancing fluids, managing electrolytes, acid-base, and nutrition. Treatment could also include renal replacement therapy, such as peritoneal dialysis. The paper also discusses the factors involved in prognosis and recovery from acute renal failure. According to the author, newborns with acute renal failure require life-long monitoring of their renal function, urinalysis, and blood pressure. Read more at Semin Perinatol (2004 April)
The adverse renal effects of prostaglandin-synthesis inhibition in the fetus and the newborn
Researchers summarized experimental animal data to produce a literature review on the adverse renal effects of NSAIDs on the developing fetus and the maturing newborn. Read more at Pediatric Child Health. (2002 Oct)
Persistent anuria, neonatal death, and renal microcystic lesions after prenatal exposure to indomethacin
A retrospective specimen study of 6 neonates who died after in utero exposure to indomethacin. Five of the 6 neonates were exposed from weeks 20 to 28 through the end of pregnancy. Renal failure and irreversible renal damage were observed in all fetuses, while oligohydramnios was reported with 2. Read more at Am J Obstet Gynecol (1994 Sep)
Oligohydramnios associated with prostaglandin synthetase inhibitors in preterm labour
An early randomized controlled trial that observed oligohydramnios in 34 of 67 (50.75%) women treated with NSAIDs beginning at a mean gestational age of 25 weeks (range 18-31.5); including 26 (70.27%) women treated with indomethacin and 8 (26.67%) women treated with ibuprofen, compared to 2 of 67 (2.99%) control subjects. Read more at British Journal of Obstetrics and Gynaecology (1990 Apr)