Which common meds put pregnant women, infants at risk?

[DrAnil]

Which common meds put pregnant women, infants at risk?

Knowing which medications are safe to prescribe for patients who are pregnant or breast-feeding can present a challenge for dental professionals.

 

 

But an article in the latest Journal of the American Dental Association can serve as a useful reference when prescribing medication for these dental patients (August 2012, Vol. 143:8, pp. 858-871).

“Healthcare professionals who are prepared with evidence-based information about the safety of medication use during pregnancy and breast-feeding can advise their patients regarding optimal medication therapy, thereby helping to ensure health outcomes for both mother and baby,” wrote study authors Mark Donaldson, BSP, PharmD, and Jason H. Goodchild, DMD.

While dental practitioners prescribe a relatively small group of medications, the authors emphasized that dentists should be familiar with the risks and benefits of five types: analgesics/anti-inflammatories, antibiotics, local anesthetics, sedatives, and emergency medications.

Drs. Donaldson and Goodchild conducted their literature review using searches of Medline, PubMed, Embase, and the Cochrane Database of Systematic Reviews; in addition, they evaluated journals, websites, textbooks, studies, reports, conference proceedings, consensus statements, and abstracts published in English. They focused specifically on the last 50 years “because much of the newer information continues to reference older, original studies.”

Pregnancy risk factors

To determine the risks associated with the use of drugs in pregnancy, the U.S. Food and Drug Administration (FDA) traditionally has classified drugs on the basis of the level of risk they pose to the fetus, Drs. Donaldson and Goodchild noted. Drugs in categories A and B are considered safe, whereas drugs in category C may be used only if the benefits outweigh the risks. Drugs in category D should be avoided except in certain exceptional circumstances, while the use of drugs in category X by pregnant women is strictly prohibited.

“The aim when prescribing medication to a pregnant patient is to balance the risks of the drug’s potential adverse effects (usually on the fetus) with the benefit (usually to the mother) of treating the disease,” the doctors wrote.

They also recommend trying to avoid prescribing medication during the pregnant patient’s first trimester, prescribing drugs that have already been used extensively by pregnant women, and prescribing the minimum dose required to obtain the desired effect.

Analgesics and antibiotics

For example, with regard to analgesics and anti-inflammatories, research has shown that taking ibuprofen during pregnancy may cause embryonic implantation disturbances and could lead to maternal pulmonary hypertension. In addition, taking glucocorticoids such as prednisone or dexamethasone during the first trimester has been associated with oral clefts. Thus, these medications have all been labeled as pregnancy risk factor C or D by the FDA.

On the basis of three large-scale epidemiologic studies, the safest analgesic in a pregnant patient is acetaminophen, according to Drs. Donaldson and Goodchild.

With narcotics such as codeine, hydrocodone, and oxycodone, oxycodone appears to be the safest with regard to pregnancy risk; it is listed as a risk factor B, while the other two are listed as risk factor C.

With regard to antibiotics, “some antibiotics (such as tetracyclines and doxycycline) can cross the placental membrane and be deposited in the embryo’s bones and teeth at sites of active calcification,” the authors wrote. Research has shown that as little as 1 gram per day of tetracycline hydrochloride administered during the third trimester of pregnancy can produce yellow staining of both primary and secondary teeth (Journal of Dental Research, July 2005, Vol. 84:7, pp. 596-602).

Another antibiotic, clarithromycin, is listed as a pregnancy risk factor C and should not be used in pregnant women except in clinical circumstances in which no alternative therapy is appropriate. All other antibiotics commonly used in dentistry — amoxicillin, azithromycin, cephalexin, clindamycin, erythromycin, metronidazole, and penicillin — are considered risk factor B.

 

        

[DrAnil]

 Anesthetics and sedatives

In general, there are no contraindications to the careful use of lidocaine with epinephrine or prilocaine in pregnant patients, although all local anesthetics used in dentistry can cross the placental barrier, Drs. Donaldson and Goodchild noted. However, while lidocaine and prilocaine are considered risk factor B, articaine, bupivacaine, and mepivacaine are all listed as risk factor C.

Most topical anesthetics used in dentistry also are listed as risk factor C, with the exception of lidocaine, which is risk factor B. Drs. Donaldson and Goodchild recommend that practitioners use benzocaine and tetracaine preparations with caution in pregnant women.

Benzodiazepines are considered quite risky for use by pregnant or breast-feeding women and their babies. The effects of using these drugs during pregnancy may lead to fetal abortion, malformations, intrauterine growth retardation, functional deficits, carcinogenesis, and mutagenesis, with the greatest risks occurring between two and eight weeks after conception. In fact, the FDA lists these medications — such as alprazolam (Xanax), diazepam (Valium), lorazepam (Ativan), midazolam (Versed), and triazolam (Halcion) — as risk factor D/X.

Two nonbenzodiazepines — zaleplon and zolpidem — are listed as risk factor C; "if a pregnant or breast-feeding patient requires an oral sedative to help her relax throughout her dental appointment, either of these agents would be preferable to the benzodiazepines," the authors wrote.

Emergency medicines

Of all the emergency medicines one might encounter in the dental office, albuterol for the treatment of asthma or other acute bronchospasms is likely the most common. Even so, albuterol is listed by the FDA as a pregnancy risk factor C, and researchers have observed an increase in the risk of congenital malformation association with the use of this drug during pregnancy.

However, because pregnant women with untreated asthma are at much higher risk of experiencing adverse pregnancy outcomes, "In an emergency situation, the benefits to the mother exceed the risk to the fetus, and this medication needs to be administered," Drs. Donaldson and Goodchild wrote.

Similar guidelines apply to several other emergency medications, they added, including epinephrine, naloxone, flumazenil, and nitroglycerin.

Breast-feeding exceptions

With the increase in the rate of breast-feeding, more patients are inquiring about the safety and potential toxicity of drugs and chemicals that may be excreted in breast milk, Drs. Donaldson and Goodchild noted.

For most drugs, the infant is exposed to a much higher concentration during pregnancy than during lactation, so if a drug is considered acceptable for using during pregnancy, it is usually reasonable to continue its use during breast-feeding, they added.

"However, there are exceptions," they emphasized.

For example, while ibuprofen and other analgesics have been found to be safe to use when breast-feeding, daily doses of more than 100 mg of aspirin should be avoided because of the associated risk of platelet dysfunction and Reye’s syndrome. With regard to narcotics, codeine is considered the safest to use while breast-feeding, according to the American Academy of Pediatrics (AAP), while hydrocodone and oxycodone carry a higher risk of causing sedation and respiratory depression in the infant.

Similar cautions apply to the use of certain antibiotics by women who are breast-feeding. All tetracyclines, including doxycycline, are excreted in breast milk, and the manufacturers of these products do not recommend taking these medications while breast-feeding to avoid potential tooth staining. The manufacturer of clarithromycin also recommends that caution be exercised when administering this antibiotic to breast-feeding women.

All other antibiotics commonly used in dentistry — amoxicillin, azithromycin, cephalexin, clindamycin, erythromycin, metronidazole, and penicillin — are considered by the AAP to be compatible with breast-feeding, with the exception of metronidazole, according to Drs. Donaldson and Goodrich. They also recommend using erythromycin with caution "as this drug is concentrated in human milk and there are documented cases of pyloric stenosis being induced in the breast-fed newborn."

With regard to anesthetics, lidocaine (with epinephrine) and prilocaine are both considered compatible with breast-feeding, according to the AAP, even in doses exceeding the maximum allowed in humans. However, articaine is not considered compatible with breast-feeding. While no studies describing the use of epinephrine during human lactation have been published, "because of its short half-life, it is unlikely that epinephrine distributes into breast milk," Dr. Donaldson and Goodchild wrote.

Similar to the recommendations involving the use of benzodiazepines by pregnant women, the AAP does not consider most benzodiazepines to be compatible with breast-feeding. However, the pump-and-discard method sometimes used for short-acting benzodiazepines such as midazolam and triazolam has been successful for some patients, the authors noted.

"Infant exposure is reduced if breast-feeding is avoided during times when the mother receives sedative medications," they wrote. "However, because relatively small amounts of the drug are excreted into breast milk, some mothers may opt to continue nursing after weighing the benefits of breast-feeding against the potential risk to the infant."

In the long run, "A trusting, open relationship between the dentist and patient is of vital importance to optimize the mother’s treatment during her pregnancy," the authors concluded. "In particular, dentists should help pregnant or breast-feeding patients understand all of the risks and benefits before they use any prescribed medication."

        

[Drsumitra]

The cellular cause of birth defects like cleft palates, missing teeth and problems with fingers and toes has been a tricky puzzle for scientists

Now Professor Emily Bates and her biochemistry students at Brigham Young University have placed an important piece of the developmental puzzle. They studied an ion channel that regulates the electrical charge of a cell. In a new study published by the journal Development, they show that blocking this channel disrupts the work of a protein that is supposed to carry marching orders to the nucleus.
Without those instructions, cells don’t become what they were supposed to become — be that part of a palate, a tooth or a finger. Though there are various disorders that lead to birth defects, this newly discovered mechanism may be what some syndromes have in common.
Bates and her graduate student, Giri Dahal, now want to apply the findings toward the prevention of birth defects — particularly those caused by fetal alcohol syndrome and fetal alcohol spectrum disorder.
"What we think might be the case is that this is the target for a few similar disorders," Bates said. "The big thing that we have right now is that this ion channel is required for protein signaling, which means that developmental signaling pathways can sense the charge of a cell. And that’s exciting for a lot of different reasons."
For example, the new study might also have implications for the battle against cancer. With cancer, the problem is that cells are receiving a bad set of instructions that tells them to multiply and spread. If they can devise a way to block the ion channel, it may stop those cancerous instructions from getting through.
"This protein signaling pathway is the same one that tells cancer cells to metastasize," Bates said. "We’re planning to test a therapy to specifically block this channel in just the cells that we want to stop."
Bates, who received her Ph.D. in genetics from Harvard, authored the study with several BYU students. The experience has already helped launch two students into prestigious graduate programs: Brandon Gassaway is at Yale for a Ph.D. in molecular biology and Ben Kwok is at Ohio State University for dental school.
The project exemplifies BYU’s philosophy that conducting world class scholarship and preparing undergraduate students for a productive career go hand in hand. A recent survey showed that 30 percent of BYU undergraduate students conduct research with a faculty mentor. Mentored research opportunities are a big reason that so many BYU graduates go on to earn Ph.D.s. National surveys reveal that over the past five years, BYU ranks fifth in the country as a Ph.D. launch pad.

 

        

[Drsumitra]

 A mother’s knowledge is essential to her children’s oral health, according to a new study.

The study determined that mothers who were better at handling stress in their environment had children with better oral health. The study also indicated that mothers with higher maternal factors when her child was age 3 produced better oral health for the child. In addition, there were more dental visits and preventative treatment administered.

The research presumes that mothers with better maternal instincts are better at noticing oral hygiene problems and the dental needs of their children. The impact is that there are lower rates of tooth decay and gum disease.

Maintaining good oral health doesn’t start when a child’s first teeth appear. It begins during pregnancy and that responsibility falls on the mother to maintain good nutrition and oral health.

The study appeared in the Journal of Dental Research. The dental records of 224 teenagers, as well as questionnaires filled out by their mothers, were used to compile the data for the study.

        

[Drsumitra]

 Now a new study has found that periodontal disease was more severe and a periodontitis diagnosis more frequent in mothers with preterm or low-birth-weight babies versus those who had full-term, normal-weight infants. However, the placental inflammatory infiltrate and bacterial profile of both groups did not differ (Journal of Periodontology, November 3, 2012).

The scientific literature has been divided, and contradictory results have been reported on the association between maternal periodontal disease and the risk of preterm birth and/or low birth weight, noted the study authors. Some researchers have proposed that periodontitis may not be causally related to negative birth outcomes and that both may result from the same hyperinflammatory and/or environmental influences in the mothers.

"From the first studies in 1996, more than 150 papers have tried to clarify this systemic relation," said lead author Francisco Mesa, DMD, from the University of Granada School of Dentistry in Spain. "My group has good relations with the maternal hospital services of my city that allowed us to investigate the topic."

Seeking an association

Dr. Mesa and colleagues wanted to determine whether periodontal clinical parameters, periodontal bacterial profiles, and inflammatory infiltrate in placental chorionic villi are associated with adverse pregnancy results.
They conducted an observational case-control study in pregnant women hospitalized in the Virgen de las Nieves University Maternity Hospital in Granada between July 2010 and March 2011. The study included 244 puerperal women: mothers with preterm birth/low-birth-weight newborns (91) and mothers with full-term, normal-weight infants who served as controls (153).

Inclusion criteria required participants to be age 18 years and older with a preterm birth (< 259 days of gestation) and/or low-birth-weight newborn (< 2500 g). The control group included women older than 18 years old with full-term gestation (≥ 259 days of gestation) and normal-weight newborn (> 2500 g).

Information was gathered from the clinical records of the mothers. Gestational age and newborn weight were obtained from neonatology department records. The authors also looked at the study participants’ sociodemographic and gynecological backgrounds.

The women’s periodontal health was assessed in a dental examination following World Health Organization recommendations for oral examinations and using the calibrated periodontal probe PCPUNC15.

Finally, the researchers collected data on placental inflammatory infiltrate in biopsies from 68 cases and 65 controls, as well as the gingival bacterial profile in mothers with periodontitis.

Microbial analysis

They found that periodontitis was more frequent in the mothers with preterm births or low-birth-weight infants (case group). It was diagnosed in 18 women in the case group versus 11 in the control group. In addition, data between the groups showed significantly worse values for all variables in the cases group.

The cases showed more bleeding, more gingival recession, and worse probing depth and clinical attachment level measurements. However, the placental inflammatory infiltrate and gingival bacterial profile (periodontal pathogen and commensal bacteria) were similar between the groups.

It has been suggested that the risk of prematurity may increase when the fetus is exposed to periodontal bacteria and an inflammatory response is generated, noted the study authors. However, microbial analysis using plate culturing allowed the study authors to identify and measure bacterial concentrations at subgingival sites, and they found no significant differences in the microbiota between the pregnant women with periodontitis in the two groups.

"No differences in anaerobic or commensal bacterial profile were found between mothers with periodontitis in the two groups," the authors noted. "Local placental factors, such as the nature of the inflammatory infiltrate and slightly higher expression of COX-2 in the women with these adverse pregnancy outcomes, may be related to a subclinical proinflammatory status that could contribute to triggering premature labor."

Although periodontal health was significantly worse in mothers with preterm birth/low-birth-weight newborns than in those with full-term, normal-weight infants, there was no difference between these groups in periodontopathogen profile or morphological changes in the inflammatory infiltrate in placental chorionic villi, the researchers concluded.

This was the first study to determine the inflammatory infiltrate in the women’s placenta with normal and adverse birth outcomes, according to Dr. Mesa.

"Our study demonstrates that the microbiological periodontal profile and the inflammatory infiltrate in mothers with periodontitis cases is similar to mothers with periodontitis controls," Dr. Mesa said. "This means that the bacteria are not a mechanism in the above-mentioned association."

The uncertainty in the findings refers to the need for more investigation in this field to reinforce the above-mentioned association, the study authors concluded.

        

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