Request to My Readers...

I have been writing posts for “Fruit of the Womb” for almost 20 months now. It continues to be a source of great fun and greater satisfaction. It has been an opportunity to refresh, review, explore, and relate my understanding and experiences regarding a profession I dearly love. However, the last several months have taken a lot out of me, physically and emotionally. I tell you this not as an apology, but to ask for your understanding. My surgery and slow recovery, my responsibilities as “Interim Chair” for our Department of Obstetrics and Gynecology, and the recent death of my brother-in-law have all taken their toll on me in different ways.

The “Chair” role has been especially taxing. Despite my training as a “Medical Scientist,” I learned a long while back that my strength was in patient care and, indeed, even the research I have done since graduate and medical school has mostly been in the ‘clinical trials’ arena. Being a chairman requires an entirely different skill set and the endless meetings are more exhausting than any 36-hour period I have ever spent on Labor and Delivery! I knew this when I took the position, told the powers that be that I did not want to be considered for the permanent job as a condition for taking the interim role, and continue to pray daily that the ‘Search Committee’ does its job quickly and well! Please, pray along with me on that score and say a LOUD AMEN!

The long and the short of this is that I have not been able to write as frequently as I would have liked recently. Even though this is not a ‘peer review’ journal, I do actually research many of the topics I have either come up with on my own or developed in response to readers’ queries. And, that takes both considerable time and energy, both of which have been rather scarce lately. I have told others with whom I work that “my brain feels like it has been sucked dry.”

I have continued to keep up with your many comments and questions and answer just about every one (that actually gets to me). It has been especially gratifying that several of the topics we have discussed (such as miscarriage, recurrent early pregnancy loss, understanding Rh-negative status and Rh-isoimmunization, cytomegalovirus infections, fetal cystic hygromas, and others) have resulted in hundreds of queries from our readers – many continuing to be generated from posts that I made at the beginning of my tenure here. Recognition of this is very important because it highlights where YOUR interests lie and where you are looking for more information or better explanation. After all, that’s what I intended for this blog at the outset and in many ways our success makes it fairly unique among ‘medical blogs’ in that regard.

In going forward, I am soliciting your help. Several topics I would like to address in the near future include: 1) Dr T’s approach to cervical cerclage; 2) Toxoplasmosis in pregnancy; 3) Twins; 4) High order multiple gestations (i.e., more than twins); 5) autoimmune hepatitis in pregnancy; 6) Understanding antepartum fetal assessment, and, perhaps; 7) Fetal heart rate monitoring, and ; 8) Stillbirth - intrauterine fetal demise. I will, eventually, try to cover all of these topics and if you have preferences for any, please let me know.

However, I would also like to know what YOU would like to hear about. It could be a very basic topic (NO QUESTION IS TOO SIMPLE) related to routine or complicated pregnancies or as complex as you think I could handle! Of course, I reserve the right to respectfully decline to respond if it is clearly outside my realm of expertise as I have done in the past. I do know my limitations, but don’t mind when you push me to them either!

Please give this some serious thought because this is YOUR site as much as it is mine. I will stay here as long as I can, but will not over stay my welcome when your interest wanes! Thanks to all of you for reading…and for what you continue to give to me….
Dr T


*******I also have another favor to ask of all our readers. Healthline has been nominated for the prestigious Webby Award in the category of “Health”.

The International Academy of Digital Arts and Sciences will choose Webby Award winners, but the People’s Choice Webby lets you decide. It’s easy:

· Simply log on to http://peoplesvoice.webbyawards.com/

· Register to vote (or log in if you are a returnee)

· After registration, click on the Web site icon and find the Living section, under which the Health category falls

· Vote for Healthline.

And be sure to pass this pass along to your friends and encourage them to vote as well!

Thanks to all of you for being such loyal readers!
Dr T*******

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Understanding Interpretation of First Trimester Screening Results

Based on the very large number of comments and questions I continue to receive related to the interpretation of the results of ‘combined first trimester screening for aneuploidy’, it is clear that there is a lot of confusion among both patients and providers alike regarding the meaning of the results and the contributions of the individual values to the actual ‘risk assessment’. My response to the two queries below may help to answer some of the questions readers may have related to this very valuable screening test…

• At Thu Apr 10, 05:39:00 AM 2008, Anonymous said…
I am 40 years old, 11 weeks pregnant by ICSI (intracytoplasmic sperm injection) and very worried. Can you please help me to understand these results (MoM?) taken 10+3 week.

PAPP-A: 1169,58 mU/L
free beta hCG: 47,40 Mg/l
NT: 2.5

The risk for Down syndrome was estimated to be 1 in 10.

Thank you!•

At Mon Apr 14, 06:02:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous Apr 10: In your case, the increased risk for Down syndrome is probably being driven by at least your age and the relatively increased NT (nuchal translucency) measurements. I cannot comment on the absolute values of the PAPP-A and hCG because I need the multiples of the median (MoM) for these to see how they might be contributing to the overall risk. Let me explain...

Maternal serum markers (in this case the free beta-hCG and the PAPP-A) steadily change as the pregnancy progresses (i.e., by weeks' gestation) and these changes are quite significant during this early part of the pregnancy while the placental tissues are rapidly proliferating. During pregnancies in which the baby is chromosomally normal, the hCG levels begin to drop toward the end of first trimester and then level off and the PAPP-A levels tend to increase gradually throughout the pregnancy. In the case of a baby with Down syndrome (trisomy 21), the hCG levels are often elevated and the difference between chromosomally normal babies and those with Down syndrome increase as the pregnancy progresses. Earlier in pregnancy, PAPP-A levels tend to be lower than normal in Down syndrome, but the difference between chromosomally normal babies and Down’s babies tends to decrease with gestational age. In the case of trisomy 18 (Edwards’ syndrome), both hCG and PAPP-A levels tend to be lower than normal.

Because of the changes in serum marker levels by gestational age, for accurate interpretation of the test results, a different reference range must be used for each week of gestation, depending on when the test is drawn. To avoid the multiple reference range problems and also to standardize test results between different laboratories, whose reference ranges also vary, a MEDIAN value for test results in normal pregnancies is determined in each laboratory for each week of gestation.

If one arranges all the numbers in a set of data from the highest to the lowest values, the ‘median’ is the number in the middle of the data set. It is not the ‘average’ or ‘mean’ of the dataset. The median is primarily used for skewed distributions and it is seen as a better indication of central tendency than the arithmetic mean. It specifiaclly helps to provide a more robust measure of ‘central tendency' in datasets that contain outlier values. For example, if you have a dataset that contains the 9 numbers (2, 2, 2, 3, 3, 3, 4, 5, 21), the median would be 3 (the fifth number, but the arithmetic mean would be 5.

Anyway, a patient's maternal serum marker results are then expressed in each laboratory as multiples of the median (MoM), rather than as a raw 'marker' concentration. It has been found that maternal weight, maternal race/ethnicity, smoking, and maternal diabetes mellitus (insulin-dependent) variably affect maternal serum marker value. Most laboratories today correct the MoM for these conditions so that a given MoM value accurately reflects the risk of abnormality. Laboratories request that information related to these conditions be included, along with the gestational age, when the specimen is submitted. There is sufficient data available now that these 'corrections' improve the reliability of the screening tests. All this is done by computer analysis of very large data bases, so I am not able to push the numbers with my own little brain!

Thanks for a good question and I hope this helps you understand your test results better.
Dr T

• At Mon Mar 31, 08:39:00 AM 2008, Anonymous said…

Dr. Trofatter,

This posting is timely as I have just received back my results of the first trimester risk assessment and was found to be ‘screen positive’ with a risk of 1 in 33 for Down's. My baby’s nuchal translucency was 1.7mm, there was a nasal bone present, my free beta-hCG was 2.43 MoM, and the PAPP-A was 0.48 MoM. I'm trying (unsuccessfully) to focus on the 97% chance that my baby is fine. I elected not to have CVS because I received my results too close to the end of the 12th week to have sufficient time to decide, so I've deferred to having an amniocentesis in 3 weeks. My question is why 32 of the 33 women will have a normal child but still have abnormal lab values? Also, can more credence be given to the blood tests or the ultrasound in having predictive value or do all receive equal weight in determining risk?Thank you for your time. I enjoy your blog very much.

• At Fri Apr 04, 07:37:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous Mar 31: The different variables (maternal age, hCG, PAPP-A, nuchal translucency, etc) are given variable weights when factored into the risk assessment and that evens varies with gestational age (as detailed in the response above). I do not know exactly how that is determined and rely entirely on the large database that we all use when we perform these studies. The reason more 'screen positive' women will actually have a "normal" baby is one of the primary downsides of a SCREENING test rather than a diagnostic test. Screening tests are valuable if they have low false negative results (in other words, they point to the possibility of an abnormality), but the trade-off is a comparatively high false positive rate.

In the case of first trimester screening, if you are "screen positive (abnormal)" it is unlikely that a baby with trisomies 21 or 18/13 will be missed and that gives you the opportunity to have a diagnostic study done that will actually rule in or rule out the abnormality. In contrast to popular opinion, good screening tests do help reduce the number of diagnostic procedures that have to be done and help to pick up abnormalities in patients who would not ordinarily be considered 'high risk' by age alone, for example, in the case of fetal chromosomal abnormalities.

Hope this helps. Best of luck to you and let us know how things turn out!
Dr T


*********Now I have a favor to ask of all our readers. Healthline has been nominated for the prestigious Webby Award in the category of “Health”.

The International Academy of Digital Arts and Sciences will choose Webby Award winners, but the People’s Choice Webby lets you decide. It’s easy:

· Simply log on to http://peoplesvoice.webbyawards.com/

· Register to vote (or log in if you are a returnee)

· After registration, click on the Web site icon and find the Living section, under which the Health category falls

· Vote for Healthline.

And be sure to pass this pass along to your friends and encourage them to vote as well!

Thanks to all of you for being such loyal readers!
Dr T********

Labels: first trimester screening, MoM, multiples of the median

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Thanks Dr. Val for Grand Rounds 4.31!

Thanks Dr Val Jones at RevolutionHealth for all the time and attention put into this week's Grand Rounds 4.31. The link to my recent post on the "Use of Fondaparinux During Pregnancy" is also much appreciated!

A growing number of women are being identified who might require or benefit from anticoagulation therapy during pregnancy. Indications include prior history of thromboembolic complications, history of recurrent early pregnancy loss, and identification of genetic or acquired thrombophilias. The treatment of choice during pregnancy is, currently, either heparin or low-molecular weight heparin. However, when drug reactions to these agents occur, we are severely limited in terms of other options for therapy. Warfarin is teratogenic in early pregnancy and newer agents do not enjoy a wide experience under these circumstances. In this post, I review the limited literature on fondaparinux (ARIXTRA) and offer some guidelines for use in pregnancy in response to a reader's excellent questions. I would certainly appreciate any feedback regarding my thoughts on this from the worldwide medical community. We are all here to learn and share ideas!

Labels: fondaparinux in pregnancy

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Use of Fondaparinux During Pregnancy

I felt the comment below from a reader deserved a more thorough response than could be accommodated under the post upon which it was left and also might be of interest to other readers and providers who frequent this site. Anticoagulation during pregnancy has become more widely used to treat, both prophylactically and therapeutically, women who have had problems with thromboembolic complications, unexplained recurrent pregnancy loss, and those who have been identified as being ‘at risk’ because of acquired or genetic thrombophilias (e.g., antiphospholipid antibody syndrome; lupus anticoagulants; Factor V Leiden; MTHFR polymorphisms; prothrombin mutations,; antithrombin III deficiency; protein C and S deficiencies, etc.). The treatment of choice in recent years during pregnancy has been either unfractionated or low-molecular weight heparins. These are used because of their efficacy and relative safety for both mother and baby (they do not cross the placenta to the fetal circulation).

However, their use is not without risks. Prolonged use of heparins can lead to reduction in bone density (osteopenia and osteoporosis), cutaneous and systemic allergic reactions (accompanied in some cases by decreased efficacy), and heparin-induced thrombocytopenias that may place the patient at risk for hemorrhagic complications. When such complications arise, alternative medications such as fondaparinux (Arixtra) have been offered as alternative therapy. Although very few of us have a vast experience with the use of this drug in pregnancy and, currently, I am not aware of recommended regimens for the same, there is a growing need and a growing body of evidence to support that use when in indicated situations. Following our reader’s comment, I provide general information related to fondaparinux and, specifically, to its use during pregnancy….


jen27 has left a new comment on your post "Tales of Two Thrombophilias":

I am so happy to have found your blog! I have another take on thrombophilia and pregnancy. I am 39 years old, first time pregnancy and presented with bilateral PE (pulmonary emboli) at 8 weeks. Was placed on lovenox--allergic! Then placed on Heparin--allergic! I am now on Arixtra and I seem to be tolerating it well. My concern is with the delivery and also with a possible amniocentesis (of course, I am high-risk for Down's). This is a new drug and my OB is has never used it before. How do we plan for delivery? He is talking about inducing me around 37 weeks to have some control over bleeding. My hematologist has not used this drug with a pregnancy before and is not sure how we should proceed. Also, I am scheduled for a possible amniocentesis in two weeks and have started to worry about internal bleeding. Any advice would be most appreciated!


Fondaparinux is not a heparin substance. It is a synthetic pentasaccharide (5-sugar) compound that has been found to be a selective inhibitor of Factor Xa. In the blood-clotting system, Factor Xa functions at the common point at which both the intrinsic and extrinsic clotting cascades come together and, therefore, it is a highly efficient inhibitor of thrombin formation and, subsequently, fibrin formation (which is the foundation upon which blood clotting occurs). Fondaparinux actually binds, quite specifically, to antithrombin III (ATIII) which then facilitates the binding of ATIII to Factor Xa, inactivating it and interrupting the clotting cascade. Interestingly, once the ATIII-fondaparinux complex binds to Factor Xa, the fondaparinux is actually released intact and can then bind with another ATIII molecule to repeat the process.

Fondaparinux is administered by subcutaneous (not intramuscular) injection. It is rapidly absorbed and reaches peak serum concentrations about 2 hours after dosing. “It has a terminal half-life of 13 to 21 h, permitting once daily dosing” and a “linear pharmacokinetic profile which exhibits minimal intrasubject and intersubject variability, suggesting that individual dose adjustments will not be required for the vast majority of the population and there will be no need for routine hemostatic monitoring.” (Bauer, et al., Cardiovasc Drug Rev 2002;20:37-52). The drug also has minimal binding to plasma proteins usually involved in drug binding, therefore, the risk of complications related to drug interactions associated with displacement of drugs that do bind to these proteins is very low. The drug is cleared intact by the kidneys so dosing regimens in patients with renal compromise must be adjusted accordingly.

In studies performed both in vitro (Lagrange ,et al., Thromb Haemost 2002;87:831-5) and in vivo (Dempfle, N Engl J Med 2004;350:1914-5) there appears to be minimal transplacental passage of fondaparinux, placing the baby at low risk for hemorrhagic complications. Furthermore, studies performed in pregnant rats and rabbits at 32 times and 65 times, respectively, the recommended human dose have not shown impairment of fertility or a teratogenic effect on the fetus, resulting in the drug being classified as "class B." However, it should be recognized that pregnant women were excluded from all controlled clinical trials conducted with fondaparinux so there are to date no controlled trials during the first trimester of pregnancy.

Indeed, there are only a few case reports published in the scientific literature (Dempfle, N Engl J Med 2004;350:1914-5; Wijesiriwardana, et al., Blood Coagul Fibrinolysis 2006;17:147-9; Mazzolai, et al., Blood 2006;108:1569-70; Harenberg, Thromb Res 2007;119:385-8; Gerhardt, et al., Thromb Haemost 2007;97:496-7). Although the drug appeared safe and was well-tolerated with no untoward maternal or fetal effects in any of these reports, and none of the few patients described developed recurrent episodes of thromboembolic disease or allergic reaction, it is hard to generalize the safety and efficacy of the drug during pregnancy based on only a handful of patients. Safety of the drug in nursing women has also not been studied to date although, again, in lactating rats, only a small amount were found in breast milk.

With all that said and done, how should fondaparinux be used during pregnancy? None of the case reports agreed on a common regimen. In most of the clinical trials leading to its approval, fondaparinux has been employed only as a prophylactic agent in the perioperative period in ‘at risk’ patients or in the acute management of a thromboembolic condition while the patient was being transferred to warfarin over the course of 5 to 9 days. For both of these indications, fondaparinux has been found to be more efficacious than either heparin or low-molecular-weight heparin and to have comparable safety profiles. It has been found that fondaparinux is associated with hemorrhagic complications if given less than 6 hours after an operative procedure.

In the case reports, various approaches to therapy during pregnancy were described. As examples, Wijesiriwardana and colleagues (referenced above) described the case of a woman who had had deep venous thrombosis in a previous pregnancy who then developed an allergic reaction to low molecular weight heparin after three weeks of therapy during a subsequent pregnancy. She was placed on warfarin until 36 weeks’ gestation and then switched to fondaparinux 2.5 mg SQ daily. The latter was discontinued the day she began induction of labor and then restarted 6 hours after her uncomplicated vaginal delivery while she was transitioned back to a therapeutic level of warfarin. Neither she nor the baby had hemorrhagic complications related to this approach, nor did she develop recurrent thrombosis during the treatment period. In the report by Mazzolai and colleagues (also referenced above), a woman with protein S deficiency, who also had a history of deep venous thrombosis and developed allergies to both heparin and low-molecular weight heparin, was treated successfully, and without complications, for 150 days during pregnancy. Either approach seems very reasonable in the patient at high risk for thromboembolic complications and hypersensitivity to heparin compounds. Indeed, judging from the safety profile of fondaparinux to date, some thought may have to be given to its use as a first-line agent under these circumstances at some point in the future.

I realize that I have been long-winded, so in fairness to our reader, I should try to answer her questions! It would be helpful, however, if I had some more information, specifically, related to her medical history and identified risk factors for her bilateral pulmonary emboli in early pregnancy. Regardless, I would offer the following suggestions: 1) Consider maternal serum screening and a ‘targeted ultrasound’ to reevaluate your risk for Down syndrome and trisomy 18 before proceeding with an amniocentesis based on your ‘age alone’ risk; 2) If you do decide to proceed with the amniocentesis, stop the fondaparinux take your last dose 24 hours before the procedure and then resume dosing 6-8 hours afterwards; 3) Unless you have or develop other risk factors, elective delivery before 39 weeks is probably not indicated (unless you have another amniocentesis to document fetal lung maturity first); 4) Since anticoagulation therapy places you at increased risk for complications related to spinal and epidural anesthesia, and the effects of fondaparinux cannot be readily ‘reversed’ in a short period of time, consider third trimester consultation with an anesthesiologist who can suggest a plan of management in the peripartum period; 5) If an induction is planned, discontinue the drug the day before and resume 6-8 hours following delivery; 6) Consider leg compression boots throughout the time you are not taking fondaparinux before, during, and after delivery to minimize your risks for deep venous thrombosis; 7) Convert to warfarin after delivery while being covered with fondaparinux until a therapeutic INR level is reached.

Thanks for a great comment Jen and best wishes for the rest of the pregnancy! Please let us know how things turn out.
Dr T

Labels: fondaparinux, heparin, lovenox, thromboembolic complications and pregnancy, thrombophilias

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Grand Rounds 4.30 at Women's Health News - Thanks Rachel!

Sincere thanks to Rachel at Women's Health News for including a link to my recent post "Pancreatic Cancer Takes Another Young Life" in this week's Grand Rounds 4.30. The post was written in memory of my brother-in-law, John Darrek Offutt, who succumbed this past week after a two year battle against pancreatic cancer.

Like ovarian cancer, pancreatic cancer is insidious in onset and is usually not recognized early in its course. More than 32,000 individuals die annually with this condition in the U.S. and most will do so within one year of the initial diagnosis. Indeed, the time from diagnosis to death is perhaps the worst of all common cancers. Median survival of untreated disease is less than 4 months and even with state-of-the-art therapy only about 6 months. Mortality at 2 years, despite advances in therapy, is greater than 95%. Currently, pancreatic cancer is the 9th or 10th most common cause of cancer in the U.S., but the 4th leading cause of cancer-related deaths in both men and women. The National Cancer Institute estimates that more than $1.5 billion is spent each year on the treatment of pancreatic cancer.

Although pancreatic cancer is most common in the ages of 60-80, my personal experience with this disease has been in men and women between the ages of 30 and 50. Symptoms leading to the diagnosis of pancreatic cancer are often subtle, nonspecific, and may precede the actual diagnosis for months before the disease is recognized. Common symptoms include vague abdominal discomfort, nausea, loss of appetite, weakness, and weight loss. In many instances, the diagnosis is not suspected until the individual actually presents with jaundice, and perhaps, itching secondary to biliary obstruction.

At the time of diagnosis, no more than 15-20% of patients have disease that is limited enough to be considered for surgical removal. The procedure most commonly performed to manage pancreatic cancer is the Whipple procedure. This is a complicated operation that has significant associated morbidity and mortality ranging between 1-3%. Even with a 'successful' operation, median survival in experienced centers is still only about 15 months and five-year survival only 20%.

As is the case in most instances of pancreatic cancer, my brother-in-law was only a candidate for chemotherapy and radiation therapy when his disease was diagnosed. After Darrek searched the internet, he was quite aware of his poor prognosis and like so many of these patients was willing to try anything that might improve his prospects for survival. He was enrolled in a clinical trial here in Greenville, South Carolina at our Cancer Treatment Center that involved direct injection of his pancreas with viral vectors carrying, I believe, tumor necrosis factor-alpha (TNF-alpha). He lived with us during the better part of 8 months while he underwent the experimental treatment and follow-up and was later begun on 'conventional' therapy.

The treatment arrested the growth of his tumor and his condition remained quite stable for almost a year. When the cancer started to regroup, he was subject to its relentless course despite the best efforts of conventional therapy to control the disease. At the time of his death, he had been on dialysis for almost nine months, had not eaten anything by mouth in two months, developed the persistent pain that accompanies this disease and is poorly responsive to narcotics, and finally a high fever that signalled deliverance from his ordeal. At his funeral, it was commented upon by his father that he never once complained or failed to say "please" when he needed help. He remained quite lucid until right before his death - fully aware of his family who watched over him and cared for him until the end.

Labels: pancreatic cancer

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Pancreatic Cancer Takes Another Young Life...

Early yesterday morning, my brother-in-law died of pancreatic cancer. He was only 44 years old. As is so often the case with this insidious and horrible disease, he was diagnosed with the condition at a time when it was already too late to do anything about it except chemotherapy – in otherwords, the tumor could not be removed surgically.

Darrek lived with us for 6 months after he found out he had pancreatic cancer while he underwent an experimental form of therapy in our cancer center. In all, he lived about 24 months after his diagnosis, time it is very unlikely he would have had without the experimental treatment. In fact, he did very well for about a year after completing the therapy with stabilization of the tumor growth, but over the past several months, as the tumor regained its momentum, he rapidly deteriorated and finally succumbed following several weeks of the pain that usually accompanies the end-stages of this disease. His passing has left me very sad and contemplative. Although we were not very close, we had very different interests and very different outlooks on life, it was a pleasure to get to know him during the time he spent with us, an opportunity we would never have had if it had not been for his medical condition.

Personally, pancreatic cancer is one of those diseases that terrifies me. When I was in medical school, the very first patient I helped to care for during my second-year surgery rotation was a young, 37 year old man who came to the local Veteran’s Hospital because “my stomach has been swelling for the past couple of weeks and I can barely breathe and now it’s hurting,” he said with a heavy southern drawl between chain-smoking drags on his cigarettes! He was a thin man who had a massively protuberant abdomen that obviously contained fluid. Back then, students were expected to actively participate in the evaluation and management of all new patients and the first thing I did with the surgery intern was to stick a needle into the man’s abdomen to draw off some of the fluid and send it down to the hospital laboratory for analysis.

Knowing that it would take days before the results would be available, I remember taking a small amount of the fluid (we always saved ‘extra tubes’ of everything!) to the little laboratory we used on the surgical ward to look at some of it myself under the microscope. I did a quick stain on the fluid and clearly remember to this day the bizarre looking cells that were present under even low power of the microscope. Neither I nor the junior resident to whom I showed this would understand the significance of our findings until later that night.

Within a few hours after admission, the patient developed severe abdominal pain. The chief resident saw the patient, felt he had developed bowel obstruction for some inexplicable reason (we had shown him the microscope slide but he had just brushed that off as irrelevant), and scheduled him for an emergency exploratory laparotomy that night. Upon incision of the abdomen, what seemed like an endless flow of fluid poured out onto the operating room table and the floor. When the flood ceased, the attending physician looked inside, shook his head, reached his hand in to explore the abdomen, took one last look at the peritoneal cavity and turned away saying, “Close him up. There is nothing we can do for this man.” He left and we all then looked as well to see the entire bowel and peritoneal surfaces studded with little white spots – metastatic implants form the cancer in his pancreas which was enlarged and hard as a rock. It was only then that we realized we had made the diagnosis by microscopy just hours before.

The incision was closed and our patient spent the last two weeks of his life in the hospital dying from his painful, metastatic disease. He never again ate a meal or smoked a beloved cigarette. I was alone at his bedside in the small, stark, VA hospital beige, dimly lit room, window cracked, the hot breeze of summer rustling the window shade and stirring what I have come to recognize as the characteristic ‘smell of cancer’ in the air, no one else present, holding his hand when he deeply sighed his last breath. I held his limp hand a few moments afterwards, then checked his pulse and left to tell the charge nurse with a tear in my eye for a man I didn’t even really know, who had served his country in the Viet Nam war, and who died by himself with no family or friends in attendance – just a second year medical student who had eagerly attacked his abdomen with a long needle at the time of his admission and had never before confronted death. Along with the sadness I recall experiencing a sense of the surreal and an almost overwhelming sense of loneliness as I tried for the first time in my own life to understand the reality of the brevity of our existence in relationship to the vastness and infinity of the universe into which we are all born…a journey I have not yet completed.

In memory of John Darrek Offutt (October 5, 1963 – April 9, 2008), I am signing off for a few days to attend his funeral in Athens, Tennessee.

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Visit Dr. Wes for Grand Rounds 4.29!

Thanks to Dr. Wes for including my post regarding the "Affect of Smoking on PAPP-A Levels in First Trimester Screening for Aneuploidy" in this week's Grand Rounds 4.29.

As has been the case in many of my recent posts, the topic was chosen based on reader's questions, comments, and concerns left under previous posts. Offering combined first trimester screening for aneuploidy is becoming a 'standard of care' in the U.S. and throughout the world. Patients must understand that this is still a screening test and not a diagnostic test and, as such, is subject to the advantages of the same (i.e., low false negative rates) as well as the disadvantages, primarily, high false positive rates. What this means is that if the risk assessment result returns "negative" there is only a small probability that the baby has Down syndrome or trisomy 18 or 13. However, if the test returns "screen positive" this does not mean the baby has one of those chromsomal abnormalities, but it does justify offering an invasive diagnostic procedure to find out for sure if the patient wants this done.

Smoking has been clearly identified as a factor that can alter the interpretation of the first trimester screen, primarily, by its dose-related lowering effects on pregnancy-associated plasma protein-A (PAPP-A) levels. Fortunately, this was recognized early enough in the accumulation of the reference database that correction for this is included in the interpretation of the test results. Of course, if all women would simply stop smoking (before, during, and after pregnancy) ***HINT,HINT***, we wouldn't have to 'fudge' the data and. perhaps, would have an even more reliable database upon which to provide accurate risk assessment!

Labels: aneuploidy screening in first trimester

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The Gonzalez Quintuplets - HAPPY BIRTHDAY!

In a very few hours, we will be celebrating a very special event – a VERY special first birthday. At about 4:00 AM (4:11-4:13 AM to be exact) on April 7, 2007, Abram, Adal, Ian, Noelani, and Nadia were delivered to Joy and Andres Gonzalez at 28 weeks gestation by cesarean section in Greenville, South Carolina. Over the course of many months, the obstetrical and neonatal teams had coordinated the planning of the big day and when “CODE 5” was called, the response and the entire “operation” went as smoothly as could be hoped for.

The babies could not have been born into a stronger or more nurturing family. As difficult and dangerous as the pregnancy was for Joy (who had delivered their first daughter, Andrea less than 18 months earlier, also by cesarean section), the past year has proven how important the power of faith, love, and friendship can be to overcoming all obstacles. The first-born, Abram, had problems following delivery that led to a year of medical complications and hospitalizations that have stressed the families resources, financially, and I am sure, personally, and may well continue to do so, but there was not one instance during that time when we were visited by Joy, Andres, and all the children that there were not smiles on their faces, optimism in their voices, and enough love in their hearts to brighten all of our spirits.

Into each of our lives come events leading to memories that we carry with us until we’re gone. That has been especially true for me in medicine. There are many patients who, unbeknownst, sometimes gave to me more than I gave to them, and I will never forget those folks. Their memories are as clear to me now as the day they happened. They are the foundation of my approach to the practice of medicine, guiding my deductive and intuitive senses, and my inspiration to awaken early every day to a new set of challenges. They have made me a better physician and a better person. Such is the case with the Gonzalez family, and I am so grateful that they have let me be a part of their lives….So, HAPPY BIRTHDAY GUYS AND GALS, and may we share many, many more together...
Dr T

Labels: Multiple gestations, quintuplets

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Elective Late Preterm Birth – Why Aren’t Patients and Providers Listening?

In several posts over the past 18 months we have discussed the neonatal (and, to a lesser, though still significant degree, maternal) risks of “late preterm” or “near term” birth especially when this is done ‘electively’ and by cesarean section prior to the onset of labor. Personally, I have spent the last two years repeating the litany at each of the local hospitals throughout our perinatal region in the Upstate of South Carolina. Recently, recognizing the importance of both patient and provider education as necessary to the success of the campaign, and with the support of the March of Dimes and our State Medicaid Office, we have sent out patient friendly brochures to all providers detailing these risks. Within the past year or so, even the American College of Obstetricians and Gynecologists has taken the firm stance of decrying elective delivery before 39 weeks without medical indication or assessment of fetal lung maturity. So, why am I writing a new post on this subject? Despite the simplicity of the message, not all patients and providers are listening or taking the commandment seriously. “Thou shalt not deliver before 39 weeks, unless thou hast a good indication.”

Ignoring the message is foolish, is associated with increased morbidity for otherwise healthy babies (usually in hospital settings not prepared to handle the unexpected – further increasing the risk of morbidity, mostly respiratory distress), and has gotten to the point where it is indefensible from a medical-legal standpoint. Late preterm birth now constitutes about three-quarters of all preterm deliveries. This amounts to more than 300,000 deliveries per year! Many of these deliveries are by elective cesarean section and many others result from cesarean section as a consequence of failed labor induction when the mother’s cervix is ‘unfavorable.’ Indeed, 50% or more of late preterm inductions end up as cesarean sections. The real tragedy is not in the delivery for appropriate medical indications that results in a baby with complications of prematurity, but the ‘iatrogenic’ prematurity resulting from inaccurate pregnancy dating or marginal medical indications such as “the baby was getting awfully big, her blood pressure was up a little at her last visit, she’s getting a lot of swelling…” and, unfortunately, as many as one-third of all late preterm births are the result of iatrogenic prematurity.

Several recently published articles contribute to the growing body of evidence supporting the concerns related to late preterm birth – whether spontaneous, medically indicated, or iatrogenic. McIntire and Leveno (Obstet Gynecol 2008; 111:35-41) evaluated neonatal outcomes at 34, 35, and 36 weeks of gestation compared with births at 39 weeks. At their institution, late preterm singleton live births accounted for 76% of all preterm births, 45% the result of the late of ‘preterm labor’ and found that ”mortality rates per 1,000 live births were 1.1, 1.5, and 0.5 at 34, 35, and 36 weeks, respectively, compared with 0.2 at 39 weeks (P<.001).” Neonatal morbidity was significantly increased at 34, 35, and 36 weeks, including respiratory distress requiring ventilator support, intraventricular hemorrhage (grades 1 and 2), need for invasive sepsis work-ups, culture-proven sepsis, hyperbilirubinemia, and necrotizing enterocolitis. Shapiro-Mendoza and colleagues (Pediatrics 2008;121:223-32) compared 26,170 infants born late preterm to 377,638 born at term and found that the late-preterm infants were 7 times (22% vs 3%) more likely to have newborn morbidity than term infants. “The newborn morbidity rate doubled in infants for each gestational week earlier than 38 weeks. Maternal medical conditions, especially, maternal hypertensive disorders and hemorrhage increased the vulnerability of the late preterm infants. Yoder and colleagues (Obstet Gynecol 2008;111:814-22) also demonstrated the gestational age-related risk for morbidity and confirmed previous observations that infants delivered by cesarean section fared worse than those delivered vaginally. The article immediately following this one by Yee and colleagues (Obstet Gynecol 2008;111:823-28) supported the relationship of elective cesarean delivery and respiratory complications and also pointed out the increased risk of male infants compared to females born prior to term.

So, what got me off on this tirade today? Well, recently, I visited our neonatal intensive care unit, and there, laid out on a bed designed for the smallest of premature babies, was another 10 lb infant, born at an outside hospital by elective cesarean section at a well-documented “38 weeks.” The baby was clearly macrosomic, had profound hypoglycemia and appeared to be the product of a diabetic mother (although that diagnosis had not been suspected during the pregnancy), was male, and had severe respiratory distress syndrome – indeed, there were real concerns that he might not survive. The sad thing about the case was that the obstetrician had called me about this pregnancy the day before the delivery and asked if it was “alright just to get her delivered by cesarean section because the baby is so big, the patient is miserable, and is begging to be delivered” and I had clearly suggested that an amniocentesis to assess fetal lung maturity be performed first in the absence of any other indication for delivery. It wasn’t done, and I do not know if my recommendation was even mentioned to the patient. I said a little prayer for the baby and, selfishly, for myself, as I left hoping that I would not be called to testify if the outcome was poor in the end….

Labels: Late preterm birth

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