Cytomegalovirus (CMV): Primary or Recurrent Infection?

Perhaps the hardest part of making the diagnosis of CMV infection during pregnancy in mother and baby is simply suspecting that it might be a problem. Certainly, if the woman develops a prolonged (weeks) febrile illness, resembling infectious mononcleosis, and that diagnosis cannot be confirmed by routine testing, then CMV should be high on the differential diagnosis. The ante goes up considerably if the mother is a young teen having her first baby (especially if she conceived shortly after becoming sexually active or changing partners), or if she works, or has another young child, in a high risk setting such as a daycare center.

CMV grows very slowly and the incubation period from the time of exposure to onset of symptoms, or asymptomatic excretion of the virus, is on the order of 4-12 weeks. Serologic testing, which we will discuss in a minute, can often help to confirm a primary infection when it is obtained coincident with maternal symptoms. Virus detection by culture, immunofluorescent techniques, or polymerase chain reaction (PCR), best done by sampling maternal urine, may be positive (and almost always will be for months after a primary infection), but this alone does not tell us if this is a primary symptomatic CMV infection or a recurrent infection accompanying another illness.

Unfortunately, since such a high percentage of primary maternal infections are asymptomatic, or simply confused with another illness, or even written off as normal symptoms of pregnancy, usually the diagnosis is not suspected until the baby is found to be growth restricted or has subtle physical abnormalities, or a thickened placenta, to suggest it has either a chromosomal abnormality or a congenital infection, sometimes months after the maternal exposure. Under these circumstances, maternal serologic testing might not be helpful in establishing either the fetal diagnosis or the diagnosis of a primary maternal infection during pregnancy.

Establishing the presence of fetal infection requires an 'invasive' procedure. Performing a simple amniocentesis, and using any of the techniques noted above for virus detection, can confirm fetal infection with CMV in nearly 100% of cases. (Remember, the amniotic fluid from midtrimester on is mostly fetal urine, and CMV is excreted in large amounts from the kidneys following congenital infection, and often for years afterwards, even in 'asymptomatic' cases). However, unless we have confirmatory maternal serologic information, or symptomatic infection confirmed to be the result of CMV during the pregnancy, we still may not know if the congenital infection is the result of primary or recurrent maternal disease. If the diagnosis of CMV is not suspected until late in pregnancy, or not until after the birth of the baby, detection of CMV in a urine sample taken from the baby within the first two weeks' of life also suffices to confirm congenital infection. CMV is a VERY slow growing virus, so any detection of virus in this time frame most certainly represents intrauterine infection.

Now let's discuss serologic testing because this is where things become even more confusing with CMV. Usually, when we contract a virus infection like the flu, our immune systems react by first producing specific antibodies to the virus of the IgM class. These usually hang around only for no more than 2-4 weeks after the infection has been cleared. Shortly after IgM antibodies begin to be made, our bodies switch to the production of a second class of specific antibodies called IgG. IgG antibodies generally hang around for a long time after the infection is cleared and provide us with a source of 'permanent immunity' to the organism, helping to prevent reinfection, or decrease the severity of a secondary infection, with the same or similar organisms with which the antibodies might 'cross-react.'It is these IgG antibodies that also afford protective immunity to the baby because they can cross the placenta whereas IgM antibodies cannot.

We can use this information to help us to characterize the status of an infection. If neither IgM nor IgG is present, the individual has probably never been exposed to the organism of concern (or is too early in the course of the infection to have mounted any antibody response). If IgM is present and there is no IgG, then the infection is probably a 'primary' infection, indicating first time exposure to the organism, usually very early in its course. If both IgM and IgG are present, this also usually reflects a primary infection, but later in the course of the disease. And, if only IgG is present, then this indicates a state of permanent immunity established from an infection that occurred at some time in the past. In any of the first three circumstances, if an infection with a specific organism is suspected and could be of concern for a pregnancy, it is probably worth repeating the antibody titers in 4-6 weeks. In the case of CMV, IgG antibodies usually can be detected by 1-2 weeks after the onset of symptomatic infections, but because of the long incubation period of CMV, this might be a month or more after actual exposure to the virus. Rising and falling antibody titers can also help to characterize the status of an infection.

With CMV infections, things are a little trickier. The presence of IgM in the absence of IgG and in the presence of symptomatic disease (or a history of recent exposure to a known carrier) is highly presumptive of a true 'primary infection.' Similarly, the findings of both IgM and IgG with a significant rise (four-fold or more) in IgG titers (with or without a fall in IgM titers) on a follow-up screen 4-6 weeks later, usually (but not always in the case of CMV) indicates a recent primary infection. Also useful, the presence of IgG in the absence of IgM, is highly suggestive of a remote exposure to the virus, often greater than 6 months previously.

The rub with serology in classifying CMV infections comes in most often when IgM is present but IgG titers are relatively stable or mildly fluctuating. Unlike most common viral infections, CMV-specific IgM can sometimes persist 6-9 months following its appearance. And to make things even more confusing, IgM has been found to reappear on occasion with reactivation of latent CMV infections. In otherwords, except in the circumstances detailed above, we may not be able to use the presence of IgM in our counseling to tell patients that they have had a primary or recurrent infection during the pregnancy or if the infection might have occurred even prior to the current pregnancy.

Ascertaining the status of a maternal infection as primary or recurrent, when we can do it, helps in counseling the patient. Babies contracting CMV as the result of recurrent infections are much less likely to suffer the severe sequelae associated with congenital CMV. Congenital CMV infections associated with primary maternal infections early in pregnancy and accompanied by growth restriction and detectable abnormalities by fetal ultrasound, generally, have a very poor prognosis, but even then, the outcome is not entirely predictable....

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Cytomegalovirus (CMV): Spectrum of Disease

From the time of exposure to CMV, to the onset of virus excretion, which occurs whether or not symptomatic disease develops, usually takes 4-12 weeks. At least half of the primary, and the vast majority of the recurrent, infections are entirely asymptomatic. Symptomatic infections often mimic 'infectious mononucleosis' (caused by another herpes virus, Epstein-Barr virus) with prolonged fever, often high and spiking, myalgia (muscle ache), arthralgia (joint pain), sore throat, and enlargement of the liver, spleen and lymph nodes. More serious manifestations can occur, but these are fortunately less common and beyond the breadth meaningful to our discussion. Pregnancy by itself does not appear to increase the risk of more severe CMV infections. However, these are more common in immunocompromised women, for example, those with HIV, organ transplants, autoimmune disorders, and cancer. Such patients are at greater risk for more frequent, symptomatic, and severe recurrent CMV infections that may also increase the fetal risk for congenital infections with unexpectedly severe manifestations.

Congenital infections occur in about 1-2% of all pregnancies accounting for 40-50,000 cases per year. Transmission of CMV to the fetus can occur with both primary and recurrent infections despite maternal immunity and has been documented in consecutive pregnancies. Primary maternal infections carry an overall transmission risk to the baby of 25-50% and recurrent infections about 2-3%. Maternal antibody is incompletely protective against transmission to the baby, but it does play a major role in reducing the severity of infection in both fetus and newborn. More than 90% of congenitally infected infants, regardless of the severity of their infection, will shed infectious virus at birth, and may do so for 6 or more years longer, even in the presence of specific immunity.

Congenital CMV infections are asymptomatic or unrecognized in about 90% of cases, including 85-90% of babies acquiring the virus as a consequence of primary maternal infection and 99% of those resulting from recurrent infections. Most of the asymptomatic infections pose no immediate life threat, but 10-15% of these babies are at risk for long-term complications such as sensorineural hearing loss, chorioretinitis, and dental abnormalities, usually apparent by two years' of age. Of these, the hearing loss is by far the most significant because delay in its detection can contribute to psychomotor retardation.

About 5-10% of congenitally infected babies will have significant evidence of infection at birth. Approximately half of these will have classic 'cytomegalic inclusion disease (CMID)' (described below) and half will have atypical involvement. Virtually 100% of these infants excrete CMV at birth and will continue to do so for many years afterwards. Infants in this group have a 20-30% eventual mortality and account for 90% of the significant mental and psychomotor retardation associated with congenital CMV infections. The most severely affected children are usually the result of primary maternal infections during pregnancy and should be suspected in instances of unexplained intrauterine growth restriction and fetal death beyond 20 weeks' gestation.

The most common findings in babies with CMID include symmetrical growth restriction, multiple small skin hemorrhages (petechiae), enlargement of the liver and spleen (hepatosplenomegaly), jaundice, microcephaly (small head), abnormalities of the dental enamel, and chorioretinitis. They can have numerous associated birth defects involving virtually any organ system, a catalog of which is not necessary for our discussion today. Prenatal detection by ultrasound of fetal growth delay and gross or subtle, nonspecific physical abnormalities of the baby may be the only clues that a congenital CMV infection has occurred. Unfortunately, these often manifest themselves only weeks or even months after fetal infection has occurred because the virus is very slow growing, and it is relatively nondestructive, compared to other herpes viruses.

In the final post on CMV, we will focus on diagnosis and counseling...

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Cytomegalovirus (CMV): Common and Confusing

Let's take a break from the PTB saga which I promise to continue soon. The other day I got a call from a physician in Louisiana who had tracked me down to where I currently live in South Carolina. The call was regarding a woman who had lost a baby 4 months ago as the result of a congenital cytomegalovirus (CMV) infection. Seems she had conceived again within 3 months of losing that first baby and was very worried about the effects CMV might have on the new pregnancy in such close proximity to the last. If you ask the average person on the street, they have never heard of CMV, and if you ask the average health care provider, they would not be able to come up with a satisfactory answer to this couple's inquiry. And, as it turns out, the answer is not entirely straightforward, so it is worth a few posts on CMV to help you gain an appreciation for this virus and its natural history before we attempt to respond to the question ourselves...

CMV is the MOST common congenitally (fetal) and perinatally (newborn) acquired virus disease in humans and the single most important infectious cause of mental retardation and congenital deafness in the U.S. and other industrialized nations. CMV is a member of the herpes family and human CMV is restricted to humans with no known animal reservoir. At least 80-90% of individuals are infected with CMV during their lives, but infection may occur in the absence of overt disease or the recognition that an illness is the result of CMV. As with other herpes viruses, once an individual is infected with CMV, periodic 'recurrences' can result from reactivation of virus replication at various sites in which the virus is latently harbored in the body. Although probably not that common, secondary infections can also occur with other strains of CMV. No cross-reactive immunity is afforded by previous infections with other herpes viruses such as herpes simplex, varicella-zoster (chickenpox), or Epstein-Barr (mononucleosis) viruses.

Transmission of the virus can occur from exposure to just about any body fluid, most commonly via saliva, respiratory, and venereal routes or by contact with infected urine or breast milk. Exposure tends to occur at earlier ages in lower socioeconomic groups, promiscuous individuals, and children at day care centers. Serologic evidence (seropositivity) of infection in women during the common childbearing years (18-35) is about 50% for those in middle and upper, and 90% in lower, socioeconomic groups. Among seronegative women, the chance of infection (seroconversion) is about 1-3% per year, however, this is as high 10-20% in women who work in day care settings and 50% in women with infected children under two years of age!

Congenital infections with CMV occur in 1-2% of ALL pregnancies meaning the virus can cross the placenta with relative ease compared to other herpes and most other common virus infections. But, as we shall see later on, congenital infection rarely results in the poor outcome noted above unless the congenital infection is the result of a primary (first time) infection in the mother during the pregnancy. Neonatal infections are commonly acquired by exposure to an infected genitourinary tract during delivery, breast milk, and saliva of family members. Infection of the newborn rarely has the serious consequences that are seen with congenital infections resulting from primary maternal disease during the pregnancy. Serious but, generally not life-threatening, neonatal infections can result under the rare situation in which primary maternal infection occurs late in the pregnancy and delivery occurs before the mother has developed immunity to the virus that could be passed along to the fetus in utero.

As a baseline, a relatively constant percentage (10-15%) of seropositive women is found to be excreting CMV from the urinary tract at any given time. The incidence of excretion tends to increase throughout pregnancy with cervical rates in the third trimester as high as 35-40%! Overall, among seronegative women, there is about a 0.5-1% risk of a primary CMV infection in each pregnancy, although this is much higher in 'at risk' groups such as day care workers, health care providers, and women with young children. Pregnancy does not appear to increase the risk of contracting CMV, nor does it place the woman at greater risk for more severe primary infections. There is some evidence though that women who do develop more severe infections (CMV mononucleosis) and those women with asymptomatic infections who are at greatest risk for transmitting the virus to their babies have qualitatively different antibody responses to CMV than women who do not.

In the next post we will look at the spectrum of maternal and fetal disease caused by CMV...

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Infection and Preterm Birth: A General Overview

For those of you who are just joining us, I have been posting a series on preterm birth (PTB) because of the magnitude and epidemic growth of the problem in the U.S. today. In the last post, we began a discussion of broad categories of risk factors. The last major categories I usually discuss with patients are infection and inflammation. In the big scheme of things, these are our greatest concerns. Not only are they the most common factors associated with 'spontaneous' PTB, but they also tend to result in the earliest deliveries and are involved in well more than half the PTBs before 32 weeks' gestation. When present, they are also associated with the greatest risk of short- and long-term morbidity for the baby.

The biochemical factors accompanying both infection and inflammation (either 'sterile' or that secondary to infection) are major contributors to the "final common pathway" of preterm labor by their diverse effects on the uterus, cervix and fetal membranes. There are a multitude of inflammatory mediators that can directly or, indirectly, by the induction of other factors such as prostaglandins, increase uterine contractility and promote cervical 'ripening.' The latter represents a transition in the composition and arrangement of connective tissue and 'ground substance' in the cervix that ordinarily is delayed until late in pregnancy, immediately preceding, or accompanying the onset labor.

In today's post, let's focus on infection. Again, for the sake of simplicity, I usually break down problems related to infection into those that are extrauterine (outside the uterus), involving anatomic structures in proximity to the uterus (bladder, bowel, cervix, and vagina), and those that are the source of secondary infection of the uterine contents. Secondary intrauterine infection can result either from initial infections of those same anatomic structures in proximity to the uterus or from infections (clinically evident or not) at other sites outside the abdomen and pelvis. It should be noted that production of inflammatory mediators can arise, depending on the organism involved, as a consequence of local tissue damage, of chemicals produced by the organisms themselves, and from nonspecific and specific immune responses to the unwelcome organisms. When high fever accompanies an infection, it may not only reflect the systemic (blood borne) presence of inflammatory mediators, but may also potentiate their action on the uterus and cervix.

The most common 'infections' we see are those caused by bacterial organisms. Many of the bacteria associated with PTB are those with which women are chronically colonized in the gastrointestinal tract or vagina. For example, during pregnancy, women are at greater risk for urinary tract infections (subject for another post). Many of the bacteria that commonly cause bladder and kidney infections, such as E. coli and Klebsiella, are normal inhabitants of the colon. The bladder sits right on top of the cervix and lower portion of the uterus. When an infection occurs in the bladder, either symptomatically or subclinically, local release of inflammatory mediators and prostaglandins may induce uterine contractions and cervical ripening which, in some instances, can progress completely unperceived by the pregnant woman until advanced, usually, irreversible changes have taken place. Although not completely understood, it is thought that the inflammatory mediators reach the uterus and cervix by direct diffusion across contiguous tissues or via transfer in common blood or lymphatic channels. It is also possible local irritation of nerve-endings in the bladder causes a more generalized activation of nerves, also enervating adjacent structures, that may initiate uterine contractions.

Although it is not feasible to discuss all of the different situations in which infection may play a role, several other scenarios can illustrate the spectrum of conditions by which infection may contribute to PTB. Gastrointestinal infections with pathogenic bacteria and, more commonly, viruses, particularly those that are accompanied by cramping and diarrhea, place the pregnant woman doubly at risk. The 'cramping' reflects conditions under which smooth muscle contractility again is increased (remember both the bowel and the uterus are made up of smooth muscle) and the diarrhea can result in dehydration and electrolyte imbalances that are independent risk factors for increased uterine activity. When fever is present, as is often the case with GI infections, this may enhance both the rate and severity of dehydration.

Other local infections, varying in severity and chronicity, can also be the source of inflammatory mediators. Examples of these include common cervical, urinary tract, and rectovaginal infections such as Trichomonas, Chlamydia, Neisseria gonorrhea, Mycoplasma, 'bacterial vaginosis,' and Group B β-hemolytic Streptococcus, and even 'yeast,' all of which may be asymptomatic, or minimally so, during pregnancy. Of these conditions, women who develop bacterial vaginosis, a shift from the normal vaginal flora to overgrowth of more pathogenic bacteria, may be at greatest risk for PTB. In contrast to these more indolent conditions, acute severe herpes simplex virus (HSV) infections, usually primary infections in women with no prior immunity to HSV, can cause intense tissue damage of the cervix, vagina, and vulva that is typically accompanied by production of large amounts of inflammatory mediators, locally, as well as systemically. Recurrent HSV infections probably are not a significant cause of preterm labor.

Primary infections at any of the sites mentioned above have the potential to infect, secondarily, the uterine contents including the placenta, the fetal membranes, or the baby and the amniotic fluid. Such infection can spread to the uterine contents by either hematogenous (blood-borne) or lymphatic channels or by direct extension from the site of infection, most often the result of ascending infection through the cervix. Of the blood-borne infections, kidney infections (pyelonephritis) and, most recently recognized, periodontal infections are probably the most common contributors. Of the ascending infections, pathogenic organisms associated with bacterial vaginosis, including a plethora of 'anaerobic organisms' that proliferate in the absence of oxygen, are perhaps the greatest offenders. Indeed, the earlier the preterm birth, the greater the likelihood that these organisms will be involved in either overt or subclinical intrauterine infections.

There are certainly many other mechanisms by which infection can result in PTB, for example, by causing fetal malformations, anemia, tissue damage (and inflammatory mediator release), and placental insufficiency, just to mention a few. But, overall these comprise only a small portion of PTBs and the complexity of the explanations required would only detract from the big picture we are trying to present here. So, let's stop for today and in our next post (or perhaps the one after), we will finish up discussing risk groups for PTB with an important, but poorly understood, category, that being inflammation not related to infection...

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Preterm Birth: Paths to Early Delivery

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"A Stitch in Time..."

Today, let’s take a break from my ‘lecture series’ on preterm birth and present a real-life patient who illustrates a scenario in which experience, technology, and timely intervention averted a tragic pregnancy outcome from PTB…

Recently, we helped care for a woman carrying twins conceived by in vitro fertilization. She had a long history of infertility associated with polycystic ovary syndrome (PCOS) and at age 38 had all but given up hope of ever carrying a pregnancy. Our infertility group, and her primary obstetrician, had sent her to us for consultation at 12 weeks’ because of her age and the multiple gestation. She had no other significant medical problems and the discussion was very straightforward. We talked about PCOS-associated risks of hypertensive disorders and gestational diabetes and we also talked about the age-related risks of fetal chromosomal abnormalities and her options for prenatal diagnosis. She was well-educated and there was little new information I could provide her with on these topics.

We then talked about fetal complications specific to twin pregnancies and finally we got around to the subject of preterm labor. In brief, I informed her that she was at greater risk for PTB, not only because of the twins, and this being her first pregnancy, but also because of her underlying PCOS for reasons that are poorly understood and unrelated to any other medical complications either she or the twins might develop during the pregnancy. My specific concern was related to a condition called “cervical incompetence” that seems to haunt infertility patients with PCOS. Of all the things we discussed, this worried her the most. After all the time (and money) it had taken to conceive, the last thing she wanted was “to deliver too early and at my age have children who have problems resulting from prematurity.” When she left that day, I scheduled her to return at about 20 weeks’ for ultrasound evaluation of the babies and her cervix.

Cervical incompetence represents loss of integrity at the internal cervical os (the junction of the cervix and the uterus) that results in progressive cervical change from the inside out. Lots of factors can contribute to cervical incompetence and we will save that discussion for another day. Before the availability of ultrasound, however, the diagnosis was almost never made before a woman had delivered prematurely, or lost one or more pregnancies, with a history of 'silent' cervical dilation, usually presenting in the advanced stages of labor, preceded by minimal painful contractions. Over the last 10 years, we have learned that ultrasound evaluation of cervical length and configuration can help to identify cervical incompetence and certain women at increased risk for premature delivery.

When our patient came back at 20 weeks,’ her baby girl and boy looked fine. Her cervix measured 42 mm in length (very good!) but “slight funneling is noted at the internal cervical os.” No cause for immediate concern or action, but with that finding, she did buy herself a follow up ultrasound. Although scheduled for the next week, she could not keep that appointment. When she did return two weeks later, she now had “U-shaped funneling of membranes in the cervical canal to within 3 mm of the external cervical os” (very BAD!). To make a long story short, she was admitted to the hospital that day and underwent placement of an emergency (“rescue”) cervical cerclage (stitch around the cervix). At the time of the surgery, “the cervix was 1-2 cm dilated and membranes were clearly visible just within the cervix.” If something had not been done at that point, she surely would have delivered extremely prematurely, probably within days. Although the surgery went well, she understood that she still wasn’t out of the woods for early delivery and complications, especially those related to infection.

There is a happy ending to this story. She eventually carried the babies to 36 weeks’ before spontaneously rupturing membranes, having the cerclage removed, and delivering two beautiful healthy children who got to leave the hospital with her two days later. Technically, she had two “near term” births, but that was so much better than losing two babies at 22 weeks or, perhaps even worse, having two babies survive at 23-24 weeks with severe sequelae secondary to their prematurity. Like I said before, in the case of PTB, every little bit helps. Multiple factors contribute to PTB, but the key to reducing rates is to successfully anticipate risks and identify specific factors in individuals that might lend themselves to timely intervention.

Labels: cerclage, cervical incompetence

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Near Term Birth: No Place for Complacency

Late preterm, or “near-term,” birth is defined as delivery between 34 and 36 completed weeks’ gestation. According to National Center for Health Statistics in 2002, approximately 60% of all preterm births were in this category. The increase in near-term births between 1992 and 2002 was the major contributor to the overall increase in PTB over this time period. Interestingly, this increase came from the Hispanic and nonHispanic White populations, rather than from the Black population which actually experienced a decrease in PTB rates. During the same time period, the rate of deliveries less than 32 weeks' remained relatively constant.

Usually, when we think about short- and long-term complications related to prematurity, this cohort of babies doesn’t show up on the x-ray screens of most healthcare providers. However, there is a growing body of evidence to suggest that these infants have “significantly more medical problems and increased hospital costs compared with contemporaneous full term infants…and may represent an unrecognized at-risk neonatal population.” (Wang, et al., Pediatrics 2004;114:372-6).

Multiple factors are correlated with the rising number of near-term births. For example, there are increasing labor induction rates for indications of maternal medical conditions (such as diabetes and hypertension), "post-dates" pregnancy (now considered anything greater than 41 weeks'), physician convenience (often, but certainly not exclusively, in underserved areas), and patient demand. There are increasing numbers of primary cesarean sections secondary to factors such as the higher induction rates (less favorable cervix to start with, maternal medical conditions, and provider and patient impatience with the induction process), medical-legal concerns of providers for fetal well-being or fetal weight (large or small), reluctance to perform operative vaginal deliveries (forceps and vacuum extraction), and also physician convenience and patient demand.

As a consequence of the rising primary cesarean rates, there are increasing numbers of repeat cesarean sections (and fewer patients willing to undergo vaginal birth after cesarean delivery (VBAC), fewer physicians willing to perform VBAC, and fewer hospitals willing to support VBAC due to staffing and medical-legal concerns). The timing of these procedures in later pregnancy is a major source of "iatrogenic prematurity" resulting from miscalculation of gestational age, complacency regarding complications of prematurity in later pregnancy, and also physician convenience and patient demand. Indeed, this has become such a big problem that a NICHD conference in March 2006 recommended "Elective cesarean delivery should not be performed prior to 39 weeks or without documentation of lung maturity because of the significant danger of neonatal lung complications."

In addition to the above, there is an increase in the number of women who have delayed child-bearing until age 35 or older, increasing the risks of complications related to infertility, hypertension, diabetes, and other underlying medical conditions. At the same time, there have been rising success rates of assisted reproductive technologies, helping women conceive (generally older women), who otherwise never would have had the opportunity to have children because of infertility or underlying medical conditions, and increasing the number of multiple gestations which, as pointed out in my last post, is an independent risk factor for PTB, particularly between 34 and 37 weeks'. Among other factors, increased stress and substance abuse certainly contribute their share to PTB at later gestational ages as well.

Consequences of near-term delivery include increased initial complications related to respiratory distress, jaundice, feeding difficulties, seizures, hypoglycemia, and sepsis that may require management (admissions and readmissions) to expensive neonatal intensive care units (Raju, et al., Pediatrics 2006;118:1207-14). At this point, we do not have good data to tell us what this means in terms of long-term medical complications, childhood development, and costs of medical and social issues that result from being delivered not quite fully done! It would not surprise me if these turn out to be much greater than previously appreciated.

The purpose of pointing out the magnitude of the problem of near-term birth is that this is one area in which we could have a rapid and significant impact on the incidence of and morbidity associated with PTB. Clearly, education of both patients and healthcare providers is the first step in this process. (For those of you interested in an in-depth evaluation of the current staus of near-term birth, two complete issues of Seminars in Perinatology, 2006;30 (1 and 2) were devoted to this topic in February and April of this year).

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Preterm Labor Day: Factors Associated with Preterm Birth

Labor Day weekend always seems to be busy for us. I think pregnant women believe it represents a celebration and expectation of delivery rather than a tribute to the average working person. And, each year I always seem to be on call to help them celebrate, I suppose as the representative of the typical working person who NEVER gets Labor Day off! This Labor Day was no different and it provided appropriate fodder for my next promised post on preterm birth (PTB): one woman with triplets and spontaneous rupture of membranes at 28 weeks’; one with placenta previa (placenta covering the cervix) and bleeding, accompanied by uterine infection, at 32 weeks; one with a history of a D&C following spontaneous abortion of her previous pregnancy who came in with premature labor at 23 weeks; and, one who delivered a 36 week baby by cesarean section for breech presentation at an outside hospital that required transfer to our neonatal intensive care unit because of respiratory distress.

These four women illustrate several of the major risk factors associated with preterm birth: multifetal pregnancy; placental abnormalities leading to midtrimester bleeding, accompanied over time by infection; possible cervical abnormality (cervical incompetence) resulting from a previous surgical procedure; and “iatrogenic prematurity” resulting from a complacent attitude toward delivery in late third trimester. (The latter is scheduled for a separate post because it is a growing problem in this country that needs to be aggressively addressed).

There are many other risk factors for PTB, for example, black race, maternal age less than 17 or greater than 35, low socioeconomic status, genitourinary tract infections, uterine abnormalities, substance abuse of any kind (tobacco, alcohol, illicit drugs), major stress, low maternal weight, obesity, lack of social supports, poor oral hygiene, to name just a few. But, one of the most important is a history of previous preterm labor or delivery or prior low birthweight baby. A woman who has one preterm delivery has a 15-20% chance of a second; and, if she has two consecutive PTBs, the risk of recurrence ranges between 30-50%! The earlier the previous PTB, the more likely there will be a recurrence. Interestingly, women who have a history of infertility are also at greater risk for PTB once they conceive.

About 40% of PTBs follow “spontaneous preterm labor,” 30% follow premature rupture of membranes, and 30% are “iatrogenic,”resulting from indicated early delivery for maternal or fetal complications, miscalculation of gestational age, or unrealistic expectations of fetal “maturity” in late third trimester (“late preterm” or “near term” births). Spontaneous PTB after 32 weeks is more often associated with increased frequency of uterine contractions, increased uterine volume secondary to multiple gestation or excess amniotic fluid (polyhydramnios), and less likely to be complicated by infection. Early preterm birth (less than 32 weeks) is often associated with infection (overt or subclinical), more frequently associated with long-term morbidity for the baby, and more likely to recur in a subsequent pregnancy. For reasons that are not well understood, it is also more common in African-Americans.

In my next post, I will explain my concerns related to "late preterm birth." Until then, see ya later....

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