This is not just a story about pregnancy woes….it really has to do with the way the American court of opinion can influence the regulation of medication. Many of you will remember the medication Bendectin, which was prescribed years ago to help control gestational nausea and pregnancy. (I took it along with 25 percent of all pregnant women! )

Bendectin was voluntarily withdrawn from the US market by the manufacturer 30 years ago. Nausea and vomiting occurs in 80% of all pregnant women between 6 and12 weeks of gestation. Roughly 1/3 of women who have nausea and vomiting of pregnancy have symptoms that are so severe that the quality of their lives and their pregnancy suffers tremendously. And 1% of pregnant women progress to a condition called hyperemesis gravidrum. Their persistent vomiting causes them to lose more than 5% of their body weight, develop an electrolyte imbalance and severe dehydration. The condition requires hospitalization, IV fluids and significant medication to stop the vomiting.

Bendectin was a medication that combined doxalamine succinate (an antihistamine) and peridoxine hydrochloride (vitamin B6) in one tablet. Between the late 1960s into the 1970s the medical journals began publishing letters reporting an association between Benedictin use and birth defects. (Well actually, at that time a general increase in reports of birth defects appeared as researches published the data that hospitals and medical organizations were releasing as they paid more attention to and recorded birth defects.) Lawsuits claiming that this product was a teratogen causing birth defects first appeared in 1980. And by the time the product was withdrawn in 1983 there were more than 300 pending lawsuits. However, as pointed out in an article in the section ” Prospective” in this week’s New England Journal of Medicine, “Courtroom testimony claiming that Bendectin was a human teratogen was markedly devoid of evidence-based corroboration”. As a result of all these lawsuits, Merrill Dow, the company that made Bendectin, withdrew the product … not because of safety issues, but because of financial concerns. The company’s insurance premiums had risen to $10 million per year which was only 3 million less than their total income from Bendectin sales.

So was Bendectin really a teratogen? In 1979 the FDA issued a talk paper stating that studies in animals as well as several large epidemiologic studies had provided no adequate evidence linking Bendectin to an increase risk of birth defects. Another review of 13 epidemiological studies found no association between Bendectin and elevated risk of birth defects. Data maintained by the birth defect monitoring programs of the CDC found that during the period from 1985 to 1987, (which was after the product was withdrawn) the incidence of birth defects was the same as that seen during the peak time of Bendectin use. There was actually an increase in the number of hospitalizations in the United States for nausea and vomiting of pregnancy in those years. It rose from 7 per 1000 live births to 16 per 1000 live births during the period from 1981 to 1987. So to make a long story short, pregnant women suffered and were more likely to be hospitalized once they did not have access to this drug.

So here’s the good news… Recently, the FDA approved Diclegis. Aside from the fact that it’s very difficult to pronounce or spell, this is a product that has the same combination of doxylamine and pyridoxine that had been marketed as Bendectin. I’m not writing this website as an advertisement for the new drug; I’m simply intrigued by the fact that the story of Bendectin demonstrates how important it is to make clinical decisions on the basis of scientific evidence and not on lawsuits. The FDA’s approval of the “new Bendectin” was based on efficacy and safety data from randomized, placebo-controlled clinical trials and took into account extensive data showing that this product is not teratogenic. Attorney-instigated lawsuits and the fear that they generate for manufacturers, physicians and patients was, in this case, finally superseded.

There are appropriate avenues to assess drugs and then there are litigious-inspired negative headlines. As physicians and patients we should prefer the former.

Most of you know about amniocentesis and chorionic villus sampling (CVS…not the drugstore!). A quick review: Since the 1960s women over 35 were told that they had an increased risk of having a child with the extra chromosomal that caused Down’s syndrome and that once pregnant this could be detected with amniocentesis. (A procedure in which amniotic fluid is withdrawn with a long needle inserted through the abdominal wall into the uterus at around 16 week’s gestation. Cells from the fluid are then cultured for 10 to 14 days and stained so that the chromosomes can be counted.) CVS procedure was developed in the 80s. (Cells obtained from the edge of the placenta are identical to those of the fetus. They can be obtained with an instrument inserted through the cervix under ultrasound guidance as early as 10 week’s gestation.They are then immediately stained and their chromosomes are counted and analyzed and in most cases allow for an early diagnosis.)

Noninvasive prenatal testing was developed in the 1970s when the first ultrasounds produced two dimensional images of the fetus in the uterus. Initially ultrasound was used for measurements to determine gestational age and later to view anatomy. And as ultrasound developed, a maternal blood test of a protein called alpha-fetoprotein was found to be associated with open neural- tube defects (spina bifida) and other fetal abnormalities if high and if low, Down’s syndrome. As these noninvasive ultrasounds and blood tests became more less expensive, “blessed” and backed by the major medical organizations, they were offered to pregnant women of all ages. Meanwhile, back at the ultrasound, engineers and radiologists improved the imaging devices, went to real time and three dimensions. This allowed physicians and their patients to view fetal cardiac, neural and skeletal development. The perinatologists also found that ultrasound in early pregnancy allowed them to measure the thickness of the tissue at the nape of the neck (nuchal fold) which could then help foretell fetal chromosomal abnormalities. This was added to the armamentarium of noninvasive prenatal testing.

This long introduction to prenatal diagnosis is my way of getting to an article in the New England Journal of Medicine that appeared in the February 27 issue. It basically is a “We have come a long way baby” introduction to a new noninvasive test using maternal blood to access fetal chromosomes. The actual fetal DNA is analyzed from small fragments of cell-freeDNA (cfDNA) that are shed from the placenta into the maternal circulation. The amount of fetal cfDNA in maternal blood increases rapidly at the onset of embryo development so that it represents about 10% of free DNA in maternal blood during the first and second trimesters. Currently a method called massive parallel sequencing (or if you care to know, next generation sequencing) which reads millions of sequences along the length of each chromosome can be used to determine abnormal fetal chromosome number (termed aneuploidy) in maternal blood.

The current study was carried out at 21 centers in the United States. Blood was collected from women with single pregnancies who were undergoing the standard screening of blood biochemical methods (which included a few more than outlined above) with or without ultrasound measurement of the nuchal fold in the fetus. The researchers compared rates of detection of certain extra chromosomes (that is three instead of two) in trisomy 21 or Down syndrome and trisomy 18 between the fetal cfDNA test and traditional tests. They then examined birth outcomes or chromosomal counts on terminated pregnancies. The series included 1914 women. Fetal cfDNA testing detected all cases of aneuploidy and the false positive rate was significantly lower than detection with standard screening.

A separate editorial in the journal predicts that a negative result in this type of maternal blood screening will help prevent the need for invasive testing. They also state that a positive test is not enough for a final prediction that the pregnancy is abnormal. Women who have a positive fetal cfDNA test will need amniocentesis or CVS to ascertain if the fetus has a triple chromosome 18 or 21. But once this test becomes less expensive, is studied in a larger group of “low risk” women and goes mainstream, the majority of pregnant women may be assured with just this blood test that, if negative, they will not have to undergo further invasive testing.

I know this was a long (and for many uninteresting) analysis of advances in prenatal testing. But for those obstetricians who spent most of their careers helping women ensure the chromosomal health of their pregnancies, and for their future patients, this is an exciting advance.

I have obsessively discussed the positive health aspects of the various forms of contraception in my newsletters over the past few years. (Clearly a part of my Planned Parenthood background!) I have also proclaimed gender health success when the Affordable Care Act (ACA) stated that after August 1, 2012, preventive health services recommended by the Institute of Medicine and endorsed by the Department of Health and Human Services would be covered by insurance companies. These services are meant to promote the development of a health system that sustains health rather than merely treats illness. The services include all FDA approved forms of contraception, the morning after pill as well as sterilization procedures. And women will now be afforded health mandated services for cervical cancer screening, screening for sexually transmitted infections, mammograms and maternity care. But as we all know, some religious organizations and private employers have demanded exemptions from providing contraception stating that this violates their religious beliefs. Many of us have been outraged. Our umbrage was beautifully voiced in a “viewpoint” article published in the May 15th Journal of JAMA. Three physicians from the Northwestern University Feinberg School of Medicine in Chicago, Illinois contributed to the article and I would like to share their arguments with you.

Like many gynecologists, I no longer deliver babies. (I do miss it, although I don’t miss the hours.) And I realize that most of my patients are not going to have to deal with decisions about delivery. But their friends, daughters, daughters-in-laws and even granddaughters may. There was a prominent article that came out in the May 8 issue of JAMA about elective cesarean delivery on maternal request (CDMR) and I thought that if this topic was important enough to warrant publication in this journal, it was worth bringing to your attention.

The prevalence of CDMR in the United States is not precisely known. In order to gather statistics about it, there has to be a diagnostic code which is used as an official indication for the procedure in order to record it as well as to bill insurance; unfortunately there is none. The author of the article stated that the prevalence of CDMR is probably less than 3% of all deliveries.. But what I felt was fascinating was that 18% of obstetricians responding to a 2006 survey from the American College of Obstetricians and Gynecologists indicated that they would prefer CDMR if they or their spouses were delivering an uncomplicated cephalic (headfirst) singleton (one baby) pregnancy at term. There was similar data from Britain that describe preference for CDMR in 10% of midwives, 21% of obstetricians, 50% of urogynecologists, and 50% of colorectal surgeons. The reasons that were cited included fear of labor, prior poor experiences with labor, concern about specific outcomes including anal and urinary incontinence, fetal injury, and need for emergency cesarean or operative vaginal delivery.

There can be complications for both methods of delivery…who said having a baby was easy or uncomplicated. After all, I and all other Ob-Gyns spent years training to help women do so. One source of concern is late term pregnancies, i..e. not going into labor at 40 weeks gestation. Data from an examination of California birth certificate recorded that 1284 stillbirths occurred among 1,653,809 pregnancies delivered between 39 and 42 weeks of gestation or 0.07764%. This suggests that 1288 CDMRs at or just before term might have prevented one stillbirth in this group.

Difficult vaginal deliveries can, as we all know, result in birth trauma, lack of oxygen to the infant’s brain and infection. But with modern obstetrics and monitoring, this has become increasingly rare. There may be a slight increase in bladder and rectal prolapse after vaginal delivery. But when it comes to urinary incontinence, a trial from Baltimore showed that although there were initial increased rates for urinary incontinence with planned vaginal delivery vs planned cesareans delivery (7.3% versus 4.5%), there were no differences between those who planned cesarean delivery and those who planned vaginal delivery when patients were questioned about symptoms two years after delivery.

On the negative side for CDMR, cesarean delivery without labor is associated with an increased risk of newborn’s respiratory complications and overly rapid heartbeat. If this occurs, the infant may have to be transferred to the NICU. The differences in respiratory outcomes between vaginal delivery and CDMR may actually be due to gestational age of birth. Often a planned cesarean section is scheduled before 39 weeks in order to make sure that the date is set and that labor doesn’t ensue before the elective schedule. There is a reason that the term “term” is so important. Prior to 39 or 40 weeks gestation, the infant’s lungs may not be completely mature. That means that although a women may want to “get it over” or choose a date that is convenient for her and her doctor’s schedules… She could delivery a premature infant (from the perspective of its lungs) and this should never be electively done before 39 weeks of gestation.

There is also a concern that cesarean section can result in a decreased chance for bonding between mother and infant especially if the baby ends up in the NICU. Studies have shown that, in general, after elective cesarean section there is less likelihood that there will be immediate breast feeding as well as decreased duration of breast feeding.

Finally, there is a concern about complications for future pregnancies in women who initially have CDMR. Results from a large NIH funded observational study show that the risks of placenta accreta (growth and invasion of placental cells into the underlying uterine wall that prevents the usual separation and delivery of the placenta) and gravid hysterectomy (hysterectomy performed at the time of delivery or in the immediate post partum stage when the uterus is still large and receiving much greater blood supply than the nonpregnant uterus) along with maternal blood loss and surgical complications, increase with increasing number of cesarean sections. Complication rates rise from 0.2% to 2.1% for placenta accreta and 0.7% to 2.4% for gravid hysterectomy in a first compared with a fourth cesarean delivery.

The current recommendations from the National Institutes of Health and the American Congress of Obstetricians and Gynecologists for planning Cesarean Delivery on Maternal Request (CDMR) are:
1. CDMR should not be planned before a gestational age of 39 weeks has been accurately determined.
2. CDMR should not be motivated by the availability of effective pain medication and management.
3. CDMR is not recommended for women desiring several children given the risks of placenta previa, placenta accreta, and gravid hysterectomy that accumulate with each cesarean delivery.

As I leave for a brief vacation over the holiday, I wonder (as do most Americans) what’s going to happen to that impending fiscal cliff. Somehow, I reassure myself our divided congress will get this settled. But I am less complacent about the outcome for healthcare in the year and years to come. Just before I got on a plane, I glanced at the New England Journal of Medicine (my reading choices are not as literate as they should be) and came across a special report titled: “Implications of the 2012 Election for Health Care- The Voters’ Perspective.”  So as we go into the new year, I thought it might be appropriate to share the results of this report with you…

Obama won! (Excuse the exclamation point.) We also now know how those who voted for him felt about health care. Here are the stats: Obama voters were three times as likely to say that healthcare was the most important problems facing the country as those who voted for Romney. Obama voters want the Affordable Care Act  (ACA, also known as Obama care) implemented and not repealed. Obama voters want a more activist federal government intervening in the US healthcare system over the next four years. Seventy eight percent of Obama voters favor implementing or expanding the ACA and having the federal government continue its efforts to ensure that most Americans have health insurance coverage. And 85% of Obama voters support having the government try to fix the healthcare system, including 55% who believe that the federal government should have more responsibility than state governments for fixing it. And, (just a few more statistics) the majority of Obama voters upholds changing the structures of the current Medicare program ( 83%) and Medicaid program (78%). Finally 8 in 10 Obama voters believe abortion should be legal in all or most cases.

Yes, we live in a democracy but that doesn’t mean that what the majority of voters favor will, indeed, be accomplished. Thirty of the nation’s 50 states will have Republican governors in 2013, many of whom may not consider the establishment of state health insurance exchanges and Medicaid expansion as their state’s mandate. It’s clear that this may become a contentious year for many reasons and healthcare may lead the “it’s not for us” list.

Meanwhile, back to the personal, each of us should do what we can to ensure our individual health. And I will try to continue to help you do this with timely information about prevention, diagnosis and health care innovations in the year to come.

I and my staff wish you a happy and healthy New Year!

I’m sure anyone who has read a newspaper in the past few months is aware of the fears that are engulfing (of should I say filling) the French women who have received silicone implants. A company in France produced a popular (and apparently not too expensive) implant termed the Poly Implant Prothese (otherwise known as PIP). It was sold in 65 countries throughout the world over the last decade and used for breast augmentation or reconstruction in more than 300,000 women. The company that made the implants was shut down by the French government for fraud in 2010. It turns out that they had been using industrial grade silicone that was (obviously) not approved for medical use. The concern was (aside from the fact that no woman wants her breasts augmented with the same stuff they use in building or road construction) that these implants were far more likely to rupture…. apparently of the 30,000 French women who have had these implants, 1,000 experienced a rupture or leak. The French are advising those women who still have PIP implants to have them removed. Other countries are deciding what to suggest and many are simply suggesting that the women discuss “what to do” with their physician.

Why has this not been a problem here in the USA? This timely question was addressed in an article in the January 14th issue of Lancet titled “Silicone breast implants: lessons from the USA.”

The silicon-gel implants that are used in our country have been FDA approved after a long and arduous history. Currently the FDA assures us that they are safe. Their approval has allowed 150,000 American women to get silicone-gel implants for breast augmentation and 46,000 women to get them for breast reconstruction in the last year alone. In 2010 after 2 days of public testimony from silicon implant manufacturers, surgeons and scientists, the FDA concluded that American women can “consent with confidence to procedures involving silicon implants, which are considered safe but with acceptable risk of local complications (rupture, tissue hardening, pain, inflammation, and infection).” (Note the same complications occur with non-silicone, i.e. saline implants.) And just to be more precise the FDA published a 63 page report assuring the safety of silicon-gel implants.

There is quite a chronicle that preceded this. Silicon-gel implants were available in the US since the early 1960’s, but not until 1976 were they regulated by the FDA. In 1988, the FDA classified them as devices (duh) that needed their safety and efficacy to be proven in order to stay on the market. They gave the manufacturers 30 months to provide the necessary data. Apparently they could not. In 1991, it was deemed that the data did not fully assess the risks and in 1992 (this s a history lesson!) the FDA imposed a moratorium on silicon-gel implants. They were only to be used for reconstruction (after mastectomy for breast cancer or redoes of bad previous implants) and not electively for augmentation until their safety was proven. Then all hell broke loose (at least litigiously) and in 1995 the biggest US class action lawsuit took place, for $4.3 billion. Subsequently, publications in peer-reviewed journals and a 400-page report of the Institute of Medicine failed to link systemic disease with silicon breast implants. The ban was lifted in 2006 and since then 2 manufacturers; Mentor and Allergan have supplied the US market. They have promised to conduct ongoing post-approval studies and are following 40,00 women for 10 years,

So right now we feel (sorry about the use of this word) that our silicon-gel implants are safe. The authors conclude with the statement that “some critics argue that the FDA’s approval process is too slow and bureaucratic” But they add “but at what cost to safety?”

I agree with them. We should expect no less.

This calls for a 101 on ovarian function: During our reproductive lives, the ovaries provide us with our essential female hormones… estrogen and progesterone which are taken up by receptors in every cell in our body. These hormones are produced through the development of primordial eggs or oocytes within the ovaries. The ovary of the female fetus is endowed with a huge number of oocytes… 6 to 7 million to be sort of exact. But by the time we are born, that number dwindles to “just” 1 million. And by the time we hit puberty, we have a paltry 400,000. Then during our reproductive years, thousands die each month (this is termed “atresia”) while one oocyte becomes a follicle that has the potential for ovulation. This dominant follicle develops for 2 weeks, producing more and more estrogen; it then extrudes an egg that can be fertilized.

Subsequent to ovulation the follicle, now bereft of its egg, is called a corpus luteum. It produces, in addition to estrogen, progesterone and together they create a lush environment in the uterinelining for potential implantation of a fertilized egg (now called a blastocyst).

At what point does all this change? Do regular cycles mean that pregnancy will occur at the “touch” of a sperm (or thousands of them)? It turns out that reproductive menopause can occur years or even a decade before hormonal menopause. There is a national trend to delay childbearing. In my practice in LA, I practically never see women under 35 who are ready to conceive. A common question posed by my patients is “How long can I wait?” or “Is it too late?” So I thought it would be appropriate to share some of the information that was recently published in the “Postgraduate Obstetrics and Gynecology” publication that is sent to me and my colleagues biweekly for continuing education.

A woman’s fertility is definitely dependent on her age. The incidence of infertility in women 20 to 24 years old is 7%; this increases to 15% between ages 30 and 34 and then to 29% in women aged 40 to 44 years.  Not only does the quantity of oocytes dwindle, but so does their quality. The rate of spontaneous miscarriage is 10% before the age of 30; it almost doubles to 18% between ages of 35 and 39 years and then rises to 54% in those older than 45. It’s not the age of the uterus that counts, but that of the eggs. If donor eggs of younger women are used, the pregnancy and miscarriage rates are the same in women younger and older than 40.

IVF success with a woman’s own eggs is dependent on the age of her eggs. (This obviously means her own age, no matter how young she looks!) According to the Society for Assisted Reproductive Technology, women between the ages of 35 and 37 have a 37.3% live birth rate, women between 38 and 40 a 28.2% live birth rate and women between 41 and 42 a 16.7% live birth rate with their own eggs.

There are several ways to assess ovarian reserve and get some reassurance as to whether the oocytes are good enough for a successful pregnancy. (By success we mean a live birth, not whether the child can get into an Ivy League school.) Simply having regular periods is not sufficient evidence.

The first test that most doctors will run is a follicular stimulation hormone (FSH) blood test. FSH is the messenger hormone produced by the pituitary. It “commands” the ovaries’ oocytes to begin the steps towards ovulation. If the estrogen level is low (which is what happens with the onset of the period), the FSH revs up and oocytes’ development takes off. Once a dominant follicle develops and it produces its estrogen, the FSH level goes down (negative feedback). If there are not enough oocytes to pass “go” and the ovary’s reserves are low, the FSH continues to be secreted in a desperate attempt to get those oocytes to do their thing. High levels of FSH in the beginning of the cycle (we usually check around day 2 or 3 after the menstrual cycle has begun) indicate poor ovarian response. And FSH will stay up permanently once the ovaries have run out of oocytes, i.e. throughout menopause. In general, the FSH level should be between 4 and 10 mIU/mL during the early part of an “ovulatory” menstrual cycle. Levels higher than 10 to 15 are considered borderline and those higher than 16 mIU/mL are considered abnormally elevated, indicating poor reserves and predicting diminished success with fertility treatment.

There are other endocrine markers that may show low ovarian reserves. One is called antimullerian hormone or AMH. It is produced by ovarian cells from 36 weeks of gestation until menopause. With menopause it decreases to undetectable levels. AMH is not affected by pregnancy or birth control pills and may be the first ovarian reserve marker that declines. Another endocrine test that can predict potential fertility issues with age is a blood test for inhibin B, a growth factor in the ovary. It rises in the beginning of the cycle and then goes down during the second half. Low levels in the early cycle indicate diminished ovarian reserve.

Finally, ultrasound may help predict the ovaries’ reserve. The number of small “ready to go” follicles can be counted and if there are 10 or less that are seen in a scan, ovarian reserve may be compromised.

If you or a family member question whether you can wait or if it’s too late to try to conceive with your own eggs (especially if you are considering expensive and potentially invasive fertility procedures); screening for ovarian reserve should be done. The easiest test is an FSH level on day 2 of your cycle. It can be done in conjunction with these other tests, but it probably remains the simplest and least expensive method of reserve determination. The question, “How many eggs are left?”, is valid for all women who want to postpone pregnancy.

So a patient comes in to my office (sorry if this sounds like the beginning of one of those bar jokes) and as part of my due diligence I update her chart with her current medications. Upon enquiring as to what she is now taking, I may be given a container of various pills with the statement “I take these once a day”. Or I might get a description of the medication “I now take the pink pills that lower cholesterol; I’m not sure of the name…it’s a small dose; it used to be yellow”. Yes, this sounds ridiculously ambiguous but it’s not her fault. The names, colors and shapes of medications are no longer stable. (And this has nothing to do with their expiration date.) At least 70% of U.S. prescriptions are generic. The good news is that they are a lot less expensive than brand prescription drugs and indeed make up less than 20% of current prescription drug costs in the U.S..

An article about our lack of pill recognition titled “Why Do the Same Drugs Look Different? Pills, Trade Dress, and Public Health” was recently published in The New England Medical Journal. I thought I would share it with you in this week’s newsletter.

The clinical effects of brand and generic medications are supposed to be the same (or according to the authors “interchangeable”) but they often look very different. Whereas a brand medication will always appear identical with each refill, generic medications can vary in size, color and shape depending on the manufacturer supplying the pharmacy. (Need I say the cheapest brands will most likely be the ones that are supplied?) They all have to be approved by the FDA, so cheaper does not mean that quality or concentration of the medication has been compromised. An example that was given in the article (along with pictures) is fluoxetine (brand name Prozac). There are at least 10 generic versions that are pharmacologically equivalent to the original drug yet they vary in their color patterns.

No, this was not done on purpose to confuse the consumer or test the memory of her physician. It turns out that color and shape-shift has its basis in U.S. intellectual-property law. Drug manufacturers have had exclusive ownership of the physical aspects of their products, including their size, shape, color, texture, aroma and flavor. These properties are considered private property under a subset of trade law called “trade dress”.  (I immediately associated this title with words like designer, exclusive and whatever other branding adjectives makes “not-off-the-rack” fashion so unique.) To be fair…. the companies that do research and development of drugs should be compensated for the tremendous costs they assume. Often millions of dollars are spent on trials that have to be abandoned, because the medications that undergo testing are not significantly effective or are found to cause serious side effects in humans.  Without pharmaceutical company development of new drugs that meet the standards that are required for FDA approval, many diseases and conditions would remain untreated and we would all suffer. (Lack of special designer clothes would obviously not have the same effect!)

There were several reasons that pharmaceutical companies were granted broad based legal protections in the mid-20th century.  There was a valid concern that counterfeit drugs would be “palmed -off” to unsuspecting patients (and even their pharmacies) if they had the same appearance and packaging as brand-name drugs. At some point, the Third Circuit Court of Appeals upheld trade-dress protection because near-identical pills would facilitate the practice of “unscrupulous pharmacists” in “substituting less expensive generic drugs for the brand name drugs prescribed without informing their customers and without passing along the benefit of the lower price.” The courts also felt that allowing trade-dress protection served a public health function by preventing the substitution of one drug that was similar but not identical to another.

The 1997 FDA guidelines for expanding direct -to -consumer advertising of prescription drugs also made the images of pills more important to the drug companies. An example is sildenafil (you know it as Viagra, that diamond shaped light blue pill.) We all know about that “little blue pill”…it has become a stand up cultural phenomenon.

But now, that legal protection has begun to unravel. In 2003, there was a legal dispute about Adderall, a medication prescribed for children with attention deficit-hyperactivity disorder. The company that first produced it in 1996 stated that the color, shape and size of various doses helped children adhere to their prescribed regimens. When a generic company (Barr) tried to copy these color schemes the court agreed to let them; after all the original company (Shire) had claimed the importance of the color trade dress.  In the tradition of “if you can’t beat them join them” over the last 5 years, brand-name pharmaceutical companies have begun to license their trade dress to the manufacturers of authorized generics. And (for a price), some generics look the same as the name brand.

The suggestion offered by the authors of the article in NEJM seems to be truly appropriate: “Instituting a more consistent and organized system of pill appearance would increase patient adherence, reduce the complexity of medical regimens, reduce medication error, and encourage the rational use of bioequivalent generic drugs.”  I would also suggest that you bring in your bottle of current drugs so that your doctor or nurse can check the name, dosage and directions for use. None of us should rely on color, shape, aroma or flavor to identify a medication… No matter what it now looks like, it should be taken as directed.

Over the years many of my patients have come in with the happy announcement that their home pregnancy test was positive, but then voice their concern: ” I drank (wine, beer, the hard stuff) before I knew I was pregnant. Does this mean that I damaged the pregnancy? Should I worry?” (This is LA, some were already planning the preschool, grade school, high school and ivy league school that the 7 week old fetus would eventually be attending and worry that her or his chances were ruined!)

Fetal alcohol syndrome has been recognized for over a century. (It obviously has been around for as long as fermented beverages have been consumed; although when I watch all those television series about 16th century nobility, the males seem to be imbibing while the erstwhile maids, women and even princesses and queens are rarely portrayed sipping wine or mead. Considering the absence of birth control, some must have been pregnant.) Full blown fetal alcohol syndrome is pretty hard to miss: it manifests as low set ears, facial changes small chin and jaw, small head circumference, joint contractures, cardiac defect, varying degrees of mental retardation, behavioral abnormalities, hyperactivity and developmental delays. This array of fetal malformations can vary but, in general, has been associated with alcohol abuse (5 or more drinks a day) that continues throughout the pregnancy. So, could a mere drink or two a week in the first trimester do harm?

This question was addressed in a study published in a 2010 British Journal of Obstetrics and Gynecology and recently reviewed in the journal titled Obstetrical and Gynecologic Survey. (The latter allows me to catch up on the myriad articles published in my field.) The article detailed a prospective study of 2900 pregnancies in Australia (where I guess alcohol is readily available) between 1989 and 1999. A 14-year follow up of the children born to the women allowed the researchers to ascertain if alcohol had been harmful to the children’s behavior and development.

During various times in their pregnancy, the women were asked if they were or had been abstaining from all alcohol or occasionally drank (up to one standard drink per week), drank lightly (2-6 standard drinks per week), moderately (7-10 standard drinks per week) or heavily (11 or more standard drinks per week). The children from their pregnancies were then studied at birth and at 2, 5, 8, 10 and 14 years. The researchers also tried to correct for variables that could influence a child’s behavior, such as maternal age and education, the occurrence of stressful events during the pregnancy, maternal smoking and the presence of the father in the home as well as family income.

The results were somewhat surprising: In this analysis, the offspring of women who drank 2 to 6 or 7 to 10 drinks per week during the first 3 months of pregnancy did not have behavior problems up to the age of 14, and in fact had better behavioral scores than the offspring of mothers who did not drink at all!
The author of the review article points out that fetal susceptibility to alcohol is now known to be partially dependent on how rapidly alcohol is metabolized by the mother. Those who metabolize it more slowly have a higher peak blood alcohol level for a longer time than “fast metabolizes”. Alcohol breakdown (not that of the drinker, but that of the intoxicant) is dependent on possessing certain alleles (or genes), called ADH1B2 and ADH1B3. (Of note ADH1B3 has a high frequency among African Americans; unfortunately, the Australian study did not report the race of their participants.) But then how many women know their alcohol allele status? So although the allele data is interesting, it probably won’t help most women’s concerns regarding their alcohol consumption, especially in early pregnancy.

Bottom line: There are many factors that influence fetal susceptibility to alcohol, and it’s certainly best to “play it safe” and just not drink during pregnancy. But the current study allows physicians to continue reassuring their patients that have drunk less than 11 drinks per week in their first trimester that this was unlikely to have caused adverse fetal affects. And I have to add…. no one can guarantee the “right” school admission

I just returned from New York, so I am in “a talk about air travel” frame of mind.  (The reason for the trip was a board meeting for Save The Children. They are doing some amazing work to help children, mothers and families in Haiti as well as the USA and developing countries around the world….please go on their website for more information.)

As usual, I felt that the flight was interminably long, the air was dry and the food….well, I won’t discuss it here, I already did a segment about microbes on the plane. But what I haven’t addressed in the past is whether it is safe for pregnant women to fly.  ACOG (the American College of Obstetricians and Gynecologists) issued a new committee opinion in October 2009. Here is a brief summary…

If there is a complication in pregnancy, it will usually occur in the first or last trimester (bleeding and miscarriage initially, premature labor and delivery the last trimester). Most commercial airlines allow pregnant women to fly up to 36 weeks. Some may be more restrictive when it comes to international flights. (I know my daughter was told she could not fly on El AL after 32 weeks and she had to bring a letter from her obstetrician to show that she was less than that on her last flight).

Air travel is certainly not recommended during pregnancy for women who have medical problems (especially cardiac) or obstetrical problems. (The latter would include bleeding, a possible impending miscarriage, pre-eclampsia, a history or risk of premature labor, a pregnancy complicated by hypertension, diabetes or failure of normal growth of the fetus). The airlines and your doctor do not want you to go into labor on a long flight, begin to hemorrhage, or rupture your membranes (even if you are the at-that time-Alaskan governor!)

All travelers should avoid dehydration and immobilization for long periods of time; we all know about the risk of deep vein thrombosis… this is even more of an issue if you are pregnant. So wear support stockings, drink plenty of water (my advice is a 6 ounces for every hour of flight), move your lower extremities (well, if you drink enough you’ll have to make frequent trips to the bathroom!), avoid restrictive clothing (no tights) and don’t consume gas-producing drinks (carbonated sodas) or foods before flying.

And remember, there is no way to predict sudden turbulence. So keep that seat belt fastened below your hipbones while seated.

Now, let’s consider radiation exposure which increases at high altitudes. The current recommendation is not to be exposed to more than 1mSv over the course of a 40-week pregnancy. Even the longest intercontinental flights will expose passengers to no more than 15% of this limit. (So round trip should be 30%.) For the “average” pregnant flier, this should not be a problem. But if you are a frequent flier or are a part of the air crew, you should check with your employer and the Federal Aviation Administration.

Final recommendation by ACOG: “In the absence of a reasonable expectation for obstetrical or medical complications, occasional air travel is safe for pregnant women.”

And I would like to add… especially if you don’t have to fly coach!