Placenta Accreta: A Growing Problem

Today's post is written in response to the questions raised by the reader below...

Anonymous has left a new comment on your post "Hypoplastic Right Heart Syndrome (HRHS): A Reader'...":

Dear Dr T

I am 40 and pregnant for the 8th time. I have 2 kids both delivered by cesarean section and have had 3 D & C's, the most recent in March 2009. My second trimester blood work at 15 weeks for my current pregnancy showed elevated hCG (2.4MoM), AFP (2.4 MoM) and inhibin A (2.3MoM). Also uE3 (estriol) was 0.59 MoM. My first trimester blood work was normal (hCG 0.9MoM and PAPP-A 1.1MoM). Amniocentesis done at 17 weeks showed no fetal chromosome problems and fetal (amniotic fluid) AFP was 1.13 MoM (which is normal). I would like to know if I am at risk of placenta accreta or worse and how easy is it to diagnose this condition by ultrasound. I have my 20 week scan next week. I was told after the second trimester blood work that I may be at risk for growth restriction but no one has mentioned placenta accreta.

Thanks, M



To M Dec 17: That is an excellent question! As we will discuss below, you are at increased risk for placenta accreta because of your multiple uterine procedures and the abnormalities of your midtrimester serum screening might just be a hint that such an abnormality of placentation has occurred.

The first question that should be addressed is what is a placenta accreta? To understand this requires a basic understanding of the uterine anatomy. The innermost lining of the uterus is called the endometrium. This is a thin layer of a variety of very hormonally responsive cells that grow, proliferate, and finally regress (resulting in a ‘period’ if a pregnancy does not occur) during the normal menstrual cycle. Under the influence of progesterone, following ovulation in the second half of the cycle, the endometrium becomes ‘decidualized’ in preparation for the reception of an early embryo if a pregnancy does occur. The embryo attaches to and burrows into the endometrium and almost immediately begins to produce the cells that will eventually become the placenta. These cells, called trophoblasts, spread out within the endometrium (but not through it) and also invade the portion of the maternal blood vessels (spiral arterioles) that are contained within the endometrium to form the large vascular bed containing mother’s blood that will eventually bathe the placental villi and supply nutritional needs to the baby.

Beneath the endometrium is the myometrium. The myometrium contains multiple thick layers of smooth muscle cells that give the uterus its ability to contract and makes up the bulk of the uterus. Outside the myometrium is another very thin layer of cells called the uterine serosa. This is contiguous with the peritoneal lining of the abdomen and isolates the uterus from other structures within the abdominal cavity. Under normal circumstances, as the placenta develops, it grows only within the endometrium and is clearly separated from the myometrium by a structure called Nitabuch’s layer and the deepest layer of the endometrium called the decidua basalis. This separation is important, because under normal circumstances, after the birth of the baby, the placenta cleanly separates from the endometrium at this level and the maternal blood vessels that have been invaded by the trophoblasts within the endometrium rapidly contract, controlling maternal hemorrhage from the placental bed. A placenta accreta occurs when the placenta grows beneath where Nitabuch’s layer and the decidua basalis should be, anchoring the placenta to the myometrium from which it cannot readily separate following the delivery of the baby. Deeper invasion into the myometrium is called a placenta increta and if the placenta invades all the way through the uterus and the serosa, this is termed a placenta percreta. Placenta accreta occurs in about 75%-80% of such cases, placenta increta in about 15%, and placenta percreta in about 5%.

There are several mechanisms one might imagine that could lead to the development of a placenta accreta in an otherwise normal pregnancy. For example, the placental trophoblasts might not be able to respond to the normal signals that limit their growth and invasiveness and/or the maternal immune system might not be able to generate the appropriate signals. However, more often, it appears that defects in the endometrium, areas in which the endometrium has been damaged, attenuated, scarred, or denuded, placing the trophoblasts in close or direct contact with tissue layers not ordinarily ‘equipped’ to limit trophoblast invasiveness, are the primary reason placenta accreta, increta, and percreta occur. Such endometrial defects are usually the consequence of a variety of uterine operative procedures including D&Cs, myomectomies, extensive surgery for endometriosis, removal/correction of congenital uterine abnormalities (Mullerian abnormalities) such as septums, and endometrial ablation, or as the result of Asherman’s syndrome. Higher parity and advanced maternal age are also associated with increased risk for placenta accreta. In recent years, cesarean section has come to the fore as the primary factor contributing to the development of placenta accreta. Indeed, there is a clear association between previous cesarean section, a placenta previa, and the risk for a placenta accreta. Almost 25 years ago, Clark and colleagues (Obstet Gynecol 1985;66:89-92) showed that the risk of a placenta previa increases with the number of previous cesarean deliveries and that women who had four or more cesareans had a risk as high as 67% for a placenta accreta.

Accompanying placenta accreta are risks for both the mother and baby during pregnancy and at delivery. Placenta accreta is associated with bleeding, usually in third trimester, premature delivery, premature rupture of membranes, and necessity for cesarean delivery. Severe hemorrhage can occur as well as uterine rupture prior to the onset of labor, resulting in risk for fetal and maternal death. Obviously, severe hemorrhage can also occur at the time of delivery, requiring transfusion with blood products and even hysterectomy. If the placenta has invaded through the uterine wall (placenta percreta) into adjacent structures such as the bladder, bowel, or the broad ligament in which the major blood vessels supplying the uterus are enclosed, this can be an extremely challenging surgical procedure, especially if there is extensive intraperitoneal scarring from previous cesarean sections.

Sometimes the diagnosis of placenta accreta is very easy to make, especially when the placenta is overlying a previous uterine scar in the lower segment, there is not a clear separation between placenta and the myometrium (uterine muscle) and there is evidence of infiltration, into or through, the uterine muscle seen by ultrasound (Lerner, et al., Ultrasound Obstet Gynecol 1995;5:198-201). More often it is not a simple diagnosis. Only a small portion of the placenta might be involved or the myometrial invasion is on the lateral or posterior uterine walls. Efforts have been made to employ MRI to help sort out the suspected diagnosis (Palacios, et al., Acta Obstet Gynecol Scand 2005;84:716-724). This is safe enough in pregnancy and can be very helpful at times. Furthermore, unexplained elevations in the serum analytes (MSAFP and hCG) in midtrimester (the question raised by our reader) can sometimes be a hint that an accreta has occurred (Hung, et al., Obstet Gynecol. 1999;93:545-50).

Review of the management options for placenta accreta is beyond the scope of today’s discussion but perhaps can be the topic for another post in the future. However, the importance of maintaining a low threshold for suspicion in patients who have the risk factors noted above, taking steps to establish the diagnosis, and careful preparation for delivery if a placenta accreta is suspected cannot be underestimated to minimize morbidity and to optimize maternal and fetal outcome.

HAPPY HOLIDAYS TO ALL!!!!!!

Dr T

Labels: elevated MSAFP, hCG, placenta accreta

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Hypoplastic Right Heart Syndrome (HRHS): A Reader's Query

Before I respond to the reader below, I wanted to explain why you have not seen much of me lately at “Fruit of the Womb.” Those of you who have followed this blog for awhile may know that I had some medical problems of my own dating back the last 6-8 months. Unfortunately, despite a good response to coronary artery angioplasty and stenting, there were blockages that were not amenable to this procedure at the time. To make a long story short, I underwent coronary artery bypass surgery Nov 21 and was just discharged from the hospital on the 28th. Believe me, not my idea of a fun Thanksgiving!!! Up until two weeks ago, despite the fact I have not been writing new material for the site, I have been busy trying to answer many of the 60-100 questions per week that readers have left on older posts. Over the next few weeks, since my recovery will take awhile, I will try to catch up on some of those who were left behind. But, I am also going to push on with new material as it arises from reader queries and from within my day-to-day experiences. Thanks for your understanding and I hope all of you have a wonderful holiday season!
Dr T

Anonymous has left a new comment on your post "Amniocentesis Q & A":

Dear Dr. T,
Thank you very much for your informative blog. I am 33 years old, first pregnancy and I had excellent first trimester screening results as follows:

Draw date: 11 weeks 3 days
Free Beta hCG (MOM):0.78
PAPPA-A MOM: 1.39
NT (mm) 1.70
Down Syndrome Risk (after screening)= 1 in 7,195
Trisomy 18/13 Risk = 1 in > 10,000

I was very happy about those results, however, during my anatomy ultrasound at 19 weeks and 5 days, a serious congenital heart defect was identified on my baby girl's heart. She has a hypoplastic right heart. At this point, it was not possible to determine whether the tricuspid valve and/or pulmonary valve are partially/fully affected. The doctor assured me, however, that they could not see the blood flowing to the lungs. In addition, the doctor also saw a ventricular septum defect (VSD), which apparently is common in Down Syndrome babies but in my case it could also potentially be associated with the baby's complex heart condition, i.e.: tricuspid atresia. No other anomalies or markers were found on the ultrasound.

After talking to the genetic counselor, my risk was increased from 1 in 7,195 to 1 in 10, that is, a 10% chance of having a baby with a chromosomal problem. I then had an amnio 3 days ago - which went fine, no cramping, no bleeding, no fluid leaking, no fever so far. I got my FISH results yesterday indicating that the baby is chromosomally normal for the anomalies tested by FISH (T21, T13, T18, X, and Y). I was ready to celebrate when the genetic counselor said that FISH accuracy is 98% because there might have been some maternal cell contamination due to blood contained in the FISH sample. She also said that this is very unlikely but then why did she have to make such a remark?

Thus, I guess my questions to you are:
(i) How reliable are FISH results in this case?
(ii) How often is such a rare complex heart defect (Hypoplastic Right Heart Syndrome) found in Down Syndrome babies?

I am trying to have some piece of mind while I await for the final amnio results. I am hoping that my baby's heart problem is isolated and not linked to a chromosomal syndrome. I am scheduled for a fetal echocardiogram next week.
Thank you very much for your time and kind help.

Congenital heart defects occur in 0.8-1.1% of ALL pregnancies which reach delivery and about 10% of babies that undergo spontaneous abortion. At least 30 to 60% of these are not detected until after the birth of the baby despite repeated ultrasound evaluations during the course of the pregnancy. Fortunately mild abnormalities (such as isolated ventriculoseptal defects – VSDs) and even many complex congenital heart defects (such as hypoplastic left heart syndrome) are not associated with easily recognizable chromosomal abnormalities. Atrioventricular (endocardial cushion defects) defects are more commonly associated with chromosomal abnormalities (as seen in 30-50% of babies with Down syndrome – trisomy 21).

Hypoplastic right heart syndrome (HRHS) is actually one of the most rare complex congenital heart conditions occurring at about 1/4 the incidence of hypoplastic left heart syndrome. HRHS seems to most often be the consequence of the development of a very small (atretic or hypoplastic) pulmonary valve Which connects the right ventricle to the pulmonary artery), resulting in a small pulmonary artery beyond that valve (necessary for transporting blood from the heart to the lungs after birth) as well as a small ventricle, small tricuspid valve, and atrium on the right side of the heart as well. During development of the heart, good blood flow through all these structures is necessary for them to achieve normal size. So the severity of HRHS depends to some extent on both the timing and the degree of the insult to the pulmonary valve - the earlier and the more severe, generally the worse the HRHS.

Babies are able to survive in the uterus because they have two physiologic shunts for blood under normal circumstances – the foramen ovale (a large opening between the right atrium and the left atrium that assures the passage of the most highly oxygenated blood from the placenta into the left ventricle and subsequently to the brain) and, the ductus arteriosus which is a vascular connection between the aorta and the pulmonary artery. Both of these connections normally close shortly after delivery and, when the fetal heart anatomy is normal, this assures good blood flow to the lungs from the right ventricle as the lungs take over control of providing the most highly oxygenated blood to the left ventricle and out through the aorta into the systemic circulation. When these connections close in a new born with HRHS, there is inadequate blood flow to the lungs and the baby becomes blue (or cyanotic) as a consequece of inadequate oxgen for its tissues…

With regard to our reader’s questions, I would have the following comments:
The FISH results will pick up about 98% of the chromosomal abnormalities for which the laboratory is set up to screen. It will NOT pick up all chromosomal abnormalities and it is unlikely to pick up by itself subtle chromosomal abnormalities (microdeletions or additions) or isolated genetic defects. It is not very likely that your baby has Down syndrome. However, there does appear to be an increased risk for having another baby with a complex congenital heart defect and this may eventually lead your geneticists to seek some of these abnormalities in your baby and in you or your spouse.

Discussion of this is beyond my level of expertise, but examples of these include: isochromosome 5p (Paulick J, et al., Prenatal Diagn 2004;24 : 371–4); interstitial deletion of chromosome 5 (Gibbons, et al, Am J Med Genet 1999;86:289-93); interstitial deletion of chromosome 2 (Sharma J, et al., Int. J Cardiol 1997; 62:199–202); deletion 22q11 (Marino, et al Genet Med 2001;3:45-8); deletion of chromosome 22q11.2 associated with thymic hypoplasia (Chaoui, et al., Ultrasound Obstet Gynecol 2002;20:546-52).

Your greater challenge will be the weeks ahead if the diagnosis is confirmed and all I would suggest at this point is that you talk extensively with the Pediatric Cardiology and Surgery teams, members of the NICU and perhaps even other couples who have had a baby with HRHS. I wish you all the best….
Kind regards,
Dr T

Labels: chromosomal abnormalities, congenital heart defects

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Metformin Use During Conception and Pregnancy

The following recent query requested my opinion regarding the safety of metformin during the periconceptual period and throughout pregnancy. Although there are not many large or comprehensive studies addressing these concerns, the bulk of the data available to us is encouraging...

Dr. T,

Quick opinion if you don't mind. As you may recall, I miscarried on 9/12. I have since seen my PCP for a regular check-up. He prescribed me Metformin….he believes based on my history, weight, blood work and family history, my body may have issues with the breakdown of sugars (i.e., type 2 diabetes but I'm not diagnosed with that). He said that it also may have some positive side effects for me including weight loss and assistance in helping me to conceive (although that doesn't appear to be a problem since I WAS able to get pregnant even though I miscarried). He says it is completely safe.

I have read mixed things online about Metformin and potential effects on babies. Namely that no known birth defects have been caused from it but that there are not many studies either. Additionally, I have read some things about it potentially causing miscarriage.

Could you please give me your opinion on this? I would like to take it as I have for a week now, because I physically feel better. I'm very scared of the effect it may have of a pregnancy and if I were to stop taking it during my pregnancy (as my doctor said this is elective as he feels it would benefit me but is not imperative for me to take). Do you know of any potential miscarriage issues with this prescription?

Thanks again for EVERYTHING!

Christe


Women with insulin resistance are at increased risk for hyperinsulinemia, type 2 diabetes, polycystic ovary syndrome (PCOS), and hyperandrogenism (increased levels of ‘male hormones’). They also are at risk for reduced fertility secondary to ovulatory dysfunction and a suboptimal hormonal milieu that may impair conception, implantation, and placentation. Pregnancy complications include higher rates of miscarriage, gestational diabetes, hypertensive disorders, preterm delivery and operative deliveries, excessive maternal weight gain, fetal macrosomia as well as growth restriction, and admission of their babies to neonatal intensive care units for a variety of reasons (Boomsa, et al., Semin Reprod Med. 2008;26:72-84). In my own experience, they also appear to be at increased risk for complications related to cervical insufficiency.

Metformin is an oral hypoglycemic (blood sugar lowering) agent whose primary affect seems to be mediated through its ability to reduce insulin resistance, thereby leading to a reduction in blood glucose and insulin levels. Metformin has also been found to have other beneficial affects, some of which appear to be independent of its hypoglycemic activity. Included among these are its effects on lipids, inflammation, hemostasis, and endothelial cell and platelet function (Anfossi G, et al. Curr Vasc Pharmacol. 2010 Jan 1. [Epub ahead of print]; Matsumoto T, et al., Am J Physiol Heart Circ Physiol. 2008;295:H1165-H1176).

In women with PCOS, “reduction of hyperinsulinemia with metformin and diet is associated not only with improvement of the biochemical endocrinopathy, but, commonly, with restoration of menstrual cycles and fertility (Goldenberg, et al, Minerva Ginecol. 2008;60:63-75).” When used in infertile women with PCOS in combination with clomiphene citrate, an ovulation-inducing drug, metformin was shown to improve improve conception rates and, perhaps, live-birth rates compared to either drug alone (Legro, et al., N Engl J Med. 2007;356:551-66). In a recent small study of 66 women with PCOS who were clomiphene resistant and underwent in vitro fertilization, those who “received metformin (until conception) showed a significantly higher number of good quality embryos and implantation rate when compared with the placebo controls (Qublan, et al., J Obstet Gynaecol. 2009;29:651-5).” They were also found to undergo fewer spontaneous abortions in early pregnancy.

Very few studies have been done in which metformin therapy has been continued throughout the pregnancy, but in those that have, the results have been encouraging. Khattab and colleagues (Gynecol Endocrinol. 2006;22:680-4) studied 200 nondiabetic women who took metformin while undergoing assisted reproduction, of which 80 stopped the drug once they conceived and 120 continued it throughout pregnancy. Demographically, both groups were similar. Miscarriage rates “in the metformin group were 11.6% compared with 36.3% in the control group (p < 0.0001; odds ratio = 0.23, 95% confidence interval 0.11-0.42).” Similarly, Nawaz and colleagues (J Obstet Gynaecol Res. 2008;34:832-7), found that “In women with PCOS, continuous use of metformin during pregnancy significantly reduced the rate of miscarriage, gestational diabetes requiring insulin treatment and fetal growth restriction.” Furthermore, no significant congenital anomaly, intrauterine death or stillbirth in any of the woman who took metformin during in this study.

To support the observations in humans and, perhaps, to provide a mechanism of action, Luchetti and colleagues (J Steroid Biochem Mol Biol. 2008;111:200-7) found in mouse studies that hyperandrogenization, such as that which occurs in PCOS, induces embryo resorption in early pregnancy and that this is correlated with reduced production of progesterone-induced blocking factor (PIBF) and increased production of cyclooxygenase-2 (COX-2) - the overall effect of these changes creating a pro-inflammatory environment. Coincident treatment with metformin is able to reverse such changes and prevent early pregnancy loss in this animal model. To further support the overall beneficial effect of metformin in human pregnancy being the result of its overall anti-inflammatory properties, Orio and colleagues (Eur J Endocrinol. 2007;157:69-73) found in nonpregnant PCOS women that metformin treatment significantly reduced WBC count and C-reactive protein (CRP), reduced androgens, reduced low density lipids, and increased high-density lipids – all contributing to a reduction in the “proinflammatory” status of those PCOS women receiving metformin.

Finally, to answer our reader’s final concerns, in all the studies we have reviewed, in no instance did taking metformin, either during conception or throughout any time frame of pregnancy, appear to have a serious deleterious affect on the babies. Although the studies have been small, there does not appear to be a greater risk for spontaneous abortion, later pregnancy loss, or congenital anomalies (Goldenberg, et al., Minerva Ginecol. 2008;60:63-75; Nawaz, et al., J Obstet Gynaecol Res. 2008;34:832-7; Qublan, et al., J Obstet Gynaecol. 2009;29:651-5; Elizur, et al., Fertil Steril. 2008;89:1595-602; Bolton, et al., Eur J Pediatr. 2009;168:203-6; Ekpebegh, et al., Diabet Med. 2007;24:253-8). Furthermore, Bolton and colleagues (Eur J Pediatr. 2009;168:203-6) have reported that metformin is actually associated with beneficial effects of fewer growth restricted (< 10th percentile) and macrosomic (> 90th percentile babies) and fewer cases of neonatal hypoglycemia requiring glucose infusion.

Labels: diabetes, insulin resistance, metformin

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Absence of Fetal Nasal Bone in Midtrimester as a Marker for Down Syndrome

Tamsen has left a new comment on your post "Amniocentesis is Not Without Risk":

I am 29 years old and am 21 weeks along. I just had an ultrasound a couple of days ago and was told that the nasal bone is not showing up which puts me at higher risk for a baby with Down Syndrome. I have yet to have someone tell me how much of an increased risk. I did not have the 1st trimester screenings as I've always said that it wouldn't make any difference but now that it's staring me in the face I am seriously considering an amniocentesis. I just wonder if I can go through the next 19 weeks wondering. Can you tell me what my risk is for a Down Syndrome baby? Thank you.
Posted by Tamsen to Fruit of the Womb at Wed Sep 02, 04:48:00 AM 2009

Previously we published a post that discussed the role of assessment of the fetal nasal bone in first trimester screening for fetal chromosomal abnormalities and, in particular, screening for Down syndrome (trisomy 21). Confirmed absence of the fetal nasal bone in first trimester has been correlated with a detection rate for Down syndrome in the range of 70% (with false positive rates dependent on maternal ethnicity – 2.2% in causcasians; 5% in Asians; and 9% in Afro-Carribeans) (Cicero, et al. Ultrasound Obstet Gynecol. 2003;21:15–18; Prefumo, et al., BJOG 2004; 111:109–112). Although determining the presence or absence of the nasal bone can clearly contribute to the risk assessment in first trimester, unfortunately, the technical difficulty of reliably obtaining an image and accurately interpreting the findings have led to more restricted use here in the U.S., even at many major academic centers.

In contrast, in midtrimester genetic screening, often done at 18-20 weeks, the finding of an absent nasal bone and to a lesser degree a hypoplastic nasal bone, is becoming more widely recognized as a major ‘marker’ for trisomy 21. In midtrimester, complete absence of the fetal nasal bone occurs in about one-third of Down syndrome babies. If a ‘short’ nasal bone (nasal bone hypoplasia), is included in the evaluation, 60% or more fetuses with Down syndrome may be detected, again with false-positive rates depending on ethnicity and the variable cut-off values for defining a “short nasal bone” in different studies (Bromley; et al., J Ultrasound Med 2002; 21:1387–1394; Bunduki; et al., Ultrasound Obstet Gynecol 2003; 21:156–160; Lee, et al., J Ultrasound Med 2003; 22:55–60; Gamez, et al., Ultrasound Obstet Gynecol 2004; 23:152–153).

One small study using 3D ultrasound found an absent nasal bone in 9 of 26 babies with Down syndrome (34.6%) and only 1 of 27 (3.4%) chromosomally normal babies, but this also meant that 9 of the 10 (90%) babies in whom complete absence of the nasal bone was found had Down syndrome (Goncalves, et al., J Ultrasound Med 2004;23:1619-27). In a recent study of 4373 babies evaluated in midtrimester, complete absence of the nasal bone was found in about 30% of Down syndrome and only 1% of chromosomally normal fetuses . (Odibo; et al., Am J Obstet Gynecol 2008;199:281.e1-281.e5). Nasal bone hypoplasia, defined in this study as <0.75 MoM, identified 47% of Down syndrome pregnancies and occurred in 6% of normal pregnancies.

So, to our reader, I cannot give a precise estimate of increased risk based on the ultrasound findings you report. However, if the ultrasound was performed by an experienced examiner and adequate images were obtained for evaluation, the complete absence of a fetal nasal bone at 21 weeks, even as an isolated finding, is disconcerting. The risk for Down syndrome could be as high as 90% and the false positive rate 5% or less. And, if you really need to know whether or not your baby is affected, an amniocentesis would be the best way to get that information. Best wishes and please let us know what you find out.
Dr T

Labels: Down syndrome, nasal bone assessment, nasal bone hypoplasia

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Urinary Tract Infections with Group B Streptococcus (GBS) During Pregnancy

The following comment was recently left on my previous post "Misunderstanding Group B Streptococcus (GBS)":

Hi - I am getting a little confused about Group B Strep (GBS) and UTI (urinary tract infection) information. Hoping you can help me clarify. I am 7 weeks pregnant and was just diagnosed with a UTI with GBS (asymptomatic - it was done as part of my first visit screen). The nurse called and wants me to start ampicillin (5oo mg 4x/day for 7 days) immediately. I have currently taken no medication (not even a tylenol) during this pregnancy (my first). I keep reading that GBS does not require treatment but then saw that it may with a UTI - I did not know symptomless UTI's were possible. I am very much wanting to not take any medication - your thoughts on this are greatly appreciated.

One of my very first posts here at “Fruit of the Womb” addressed Group B Streptococcus (GBS) infections and pregnancy. This is a topic that is worth revisiting periodically and the questions from today’s reader raise concerns that are shared by many women during pregnancy.

GBS is a bacterium that colonizes the urogenital and lower gastrointestinal tracts in as many as one-third of all healthy reproductive age women. It is the leading cause of serious bacterial infection in newborns and is often transmitted to babies at the time of delivery. Indeed, 8,000-12,000 babies per year in the U.S. will develop complications related to GBS and approximately 2,000 infants will die from their infections. There are several well-known situations in which babies are at increased risk for developing a serious GBS infection including:

• Premature labor or rupture of membranes before 37 weeks
• Prolonged rupture of membranes (18 hr or longer) before delivery
• Fever in labor (100.4F or higher)
• History of GBS urinary tract infection during the pregnancy (4-fold risk)
• Previous baby affected by GBS disease (increases risk 10-fold!!!)

Today’s reader had an asymptomatic UTI with GBS detected at her first prenatal visit during routine screening. We do NOT know why some people carry GBS and others do not, and we are not entirely clear why far more women actually carry the bacterium than are at risk for having a baby with a serious complication related to it, although the maternal immune response to the bacterium probably plays a key role. However, we do know that GBS UTIs place women in one of the highest risk categories for pregnancy complications (preterm labor; premature rupture of membranes; subclinical premature cervical change in the continuum of ‘cervical incompetence’; chorioamnionitis) and for transmission of GBS to the baby at the time of delivery and even prior to the onset of labor (CDC, MMWR May 31, 1996;45:1-24 ). Interestingly, women with GBS UTIs are also at greater risk for hypertensive disorders in pregnancy, anemia, and for babies that are not only premature, but ‘small for gestational age’ (Schieve, et al., Am J Public Health 1994;84:405-410).

UTIs caused by GBS occur in about 5% of women. Many women are asymptomatic or confuse symptoms of pregnancy with subtle symptoms of urinary tract infections (pressure; suprapubic discomfort; frequency; and urgency). However, asymptomatic UTIs can still subject the pregnancy to the risks of the complications mentioned above. Even after treatment, asymptomatic or symptomatic UTIs will recur in as many as one-third of all pregnant women. The source of the ‘reinfection’ is usually the patient’s own lower gastrointestinal tract in which antibiotic therapy of the UTI is ineffective at eradicating colonization. Women with GBS UTIs are usually considered to be more heavily colonized and are at greater risk for persistent and recurrent GBS infections (CDC, MMWR August 16, 2002;51:1-22). They are also at greater risk for developing significant bladder and kidney infections (pyelonephritis), the latter of which may occur in as many as 50% of women who begin with an untreated ‘asymptomatic’ UTI and can be life-threatening, leading to sepsis, adult respiratory distress syndrome (ARDS), and even death during pregnancy. It is the current recommendation that women with symptomatic or asymptomatic GBS UTIs detected during pregnancy should be treated at the time of diagnosis (CDC, MMWR May 31, 1996;45:1-24).


There are 5 major serotypes of GBS (Ia, Ib, II, III, and V). All are capable of causing both maternal and neonatal disease. Babies born to women who do not have antibodies to types II and III seem to be at greater risk for complications. Indeed, at some point, this may be one of the primary factors we can use to differentiate pregnancies at risk from those which are less so. A recent study has shown that serotypes V, Ia, and III are most often associated with asymptomatic and symptomatic UTIs (Ulett, et al., J Clin Microbiol. 2009;47:2055-60). About two-thirds of serious GBS infections are apparent at the time of delivery and 90% of babies who will develop complications do so within the first 48 hr after delivery. This is generally referred to as “early-onset” GBS infection and technically is used to define disease occurring in the first week of life. “Late-onset” disease, frequently associated with serotype III, affects another 10% of newborns, often presents as meningitis with septicemia, and rarely occurs after one month of age. Up to one-third of the survivors of GBS meningitis will develop long-term physical and/or neurological handicaps and in 1 of every 8 of these babies, the handicaps will be severe.

Unless you are in one of the high risk groups noted above, the goal of prophylactic antibiotic therapy during labor in those who are found to be colonized with GBS during their pregnancies is to deliver antibiotics to the mother early enough in the course of labor that sufficient drug can be transferred across the placenta to achieve protective levels in the baby prior to birth. That means, the antibiotic selected must not only be able to kill GBS, but it must also be able to cross the placenta. Fortunately, GBS has not yet been found to have developed resistance to the antibiotic of choice, penicillin G, and this drug also readily crosses the placenta. It also has a long and proven safety record for the baby. Ideally, antibiotic therapy is begun, intravenously, at least 4 hr prior to delivery so that at least one or two doses can be administered before the baby is born. If a woman has a serious allergy to penicillin, other options for therapy exist and the risks and benefits of these are discussed in our previous post on this subject.

The important things are that your doctors did the right thing by screening you, they have identified a potential problem, and there is a well-proven means of significantly reducing the risks from that problem for both you and your baby during your pregnancy and at the time of your labor and delivery. Thanks for reading and for the good questions. Best wishes for the rest of your pregnancy!
Dr T

Labels: GBS and pregnancy, Group B Strep, urinary tract infection, UTI

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