Source # 1: Lyme Disease by Patricia Coyle of State University of NY

Chapter 23 Lyme Disease in Pregnancy
Genevieve Sicuranza and David Allen Baker
Lyme borreliosis became a reportable disease in the United States in 1982, and
in 1991 a national surveillance case definition was established. The Centers
for Disease Control in its June 1991 report indicated an eighteenfold increase
in the number of cases from 1982 through 1989(13,500). Lyme disease was first
described in 1977 in Old Lyme, Connecticut, as a juvenile-arthritis type
syndrome associated with tick bites.'(ref 12) Although cases are concentrated
in the northeastern, midwestern, and Pacific United States, Lyme disease has
now been reported from most states. It is clearly an international problem,
with a marked increase in infected and symptomatic people in Europe and Asia as
well. Due to the rising numbers of cases each year, there has been increasing
concern about the potential impact of Lyme disease on the pregnant woman and
her fetus.
Lyme disease is caused by a spirochete, Borrelia burgdorferi, classically
carried by the deer tick, hodes dammini.(ref10) Other vectors have been
identified in New Jersey and Texas (Amblyomma americanum). (ref 11) Although
the deer is the preferred host of the adult tick, almost any bird or domestic
animal can act as an intermediate host. It is known that the fetus is quite
vulnerable to the transplacental passage of the syphilis spirochete, Treponema
pallidum. Because the causative agent of Lyme disease is also a spirochete,
there is concern that B. burgdorferi might also affect the fetus. This chapter
reviews the available information pertaining to Lyme disease in pregnancy and
discusses the diagnosis and management in this selected population. (See Color
Plate 8.)

PREGNANCY
Maternal infection may involve transmission of the invading microorganism to
the fetus. This may have no adverse consequences or may produce a range of
sequela from minor transient problems to fetal death and abortion. Among the
spirochetal bacterial infections, syphilis is known to cause abortion,
stillbirth, and congenital abnormalities. Maternal relapsing fever and
leptospirosis have also been associated with an increased risk of fetal loss.

Among animals, borreliae have been associated with bovine abortion. Whether
Lyme disease affects the pregnancy or the fetus has been a subject of several
studies. In 1985, Schlessinger (ref 8) documented transplacental transmission
of B. burgdorferi for the first time. The infant involved showed congenital
heart anomalies. An autopsy revealed numerous spirochetes in the spleen, kidney
and bone marrow. The chorionic villi had histologic evidence of involvement
with increased numbers of Hofbauer cells. The mother in question had been
infected during the first trimester and had not received treatment. The Centers
for Disease Control conducted a retrospective study on 19 women with Lyme
disease. (ref 5) There were five poor outcomes:
prematurity. cortical blindness, fetal demise, syndactyly, and rash. No
association was noted between a poor outcome and the trimester in which
infection occurred, or whether treatment was given. A second study conducted by
the Centers for Disease Control (ref 5) involved a prospective analysis of 17
females infected during the first trimester. In this small prospective study,
one infant was born with syndactyly and there was one spontaneous loss at 13
weeks. All the other pregnancies resulted in normal infants.
From 1986 through 1987, Nadal et a (ref 17) surveyed over 1000 mothers at
deliveries where anti-B burgdorferi antibody titers were obtained. ** see
note below
Of these 1000 mothers, 12 had elevated titers, but only one mother was
symptomatic with Lyme disease during her first trimester. Her child was born
with a ventricular-septal cardiac defect (VSD). None of the children born to
mothers with a positive titer had detectable antibodies. Of the 12 mothers with
positive titers, 8 delivered at term, 2 were preterm and 2 were postterm. Seven
infants had problems in the newborn period: there were two cases of
hyperbilirubinemia and one case each of hypotonia; (attributed to medication),
microcephaly, supra-ventricular extrasystoles, VSD, and small for gestational
age when examined between 9 and I7 months of age; however, only the child with
the VSD remained abnormal.

MacDonald published two papers regarding
Lyme disease in pregnancy. He described four cases of fetal borreliosis found
while prospectively studying abortuses.(ref 4) His findings included one term
stillbirth and three second-trimester losses. One of the second-trimester
losses was complicated by toxemia and another by systemic lupus erythematous.
B. burgdorferi was cultured from the fetal liver in each case. From the term
stillbirth, spirochetes were found in the liver, heart, adrenal, brain, kidney,
meninges, and subarachnoid. Three of the cases had identifiable cardiac
malformations:
atrial-septal defect, VSD, and coarctation of the aorta. He questioned whether
or not B. burgdorferi could be a cause of fetal demise, congenital heart
defect, or fetal loss after toxemia. In l989, MacDonald described several other
cases. One was a 25-year-old black woman at term in labor who delivered a male
fetus who was small for gestational age with multiple anomalies including VSD
in addition to central nervous system (CNS) anomalies. B. burgdorferi was
identified in the fetal autopsy. Another was a term intrauterine
growth-retarded infant who succumbed to a large VSD and absence of the left
hemidiaphragm. This autopsy also found spirochetes in tissue. MacDonald also
reports several second-trimester losses, with and without anomalies, that at
autopsy revealed B. burgdorfen. In the same article, MacDonald refers to a
retrospective study of 10 sudden infant deaths; he reported that 2 had
spirochetes consistent with B. burgdorferi in the brain. No other laboratory,
however, has confirmed this high report of spirochetal invasion of the fetal
and placental tissue.
In contrast to these reports of MacDonald, (ref 3,4) the Fourth International
Conference on Lyme Borreliosis held in Stockholm in June of 1990 concluded that
there is little risk to the fetus.(ref 9) The symposium examined a large
retrospective study in which there was no increased rate of congenital
malformations in infants with seropositive mothers. The symposium referred to a
study in which there were six pregnant women with Lyme disease, all of whom had
healthy infants. Another study, which surveyed pediatric neurologists in areas
highly endemic for Lyme disease, failed to discover any (??!!) records of
neurologic cases that could be attributed to Lyme disease.
In a series of 143 pregnant women from Wisconsin, titers for B. burgdorferi
exposure were examined and correlated with pregnancy outcome. In the group, the
incidence of first-trimester spontaneous abortions was no greater for
seropositive women than for seronegative women.

DIAGNOSIS
According to the Centers for Disease Control (ref 5) a diagnosis of Lyme
disease in pregnancy can be made with certainty if erythema migrans (EM) is
present or if there is the new onset of typical neurologic, cardiac, or joint
involvement in a pregnant woman accompanied by laboratory confirmation of
infection (typically diagnostic antibody levels or a significant rise in acute
versus convalescent antibody levels; isolation of spirochetes from a clinical
sample is also acceptable). In reality, however, patients in whom there is a
reasonable
clinical suspicion for Lyme disease warrant treatment.

TREATMENT
According to the Centers for Disease Control, any pregnant woman with the
diagnosis of Lyme disease, or the suspicion of it, should be treated.(ref 5)
The diagnosis should be a clinical one and not based on serology because
serologic conversion may occur too late in the disease process. The problems
with current antibody assays, and the problem of seronegativity, are addressed
in Chapters 14 and 25. In the Centers for Disease Control study, 3 of
13 patients treated had abnormal fetal outcomes (23%), as did 2 of the 6
patients who were not treated (33%). According to their study, the time of the
disease in relation to poor outcome and whether the patient was treated were
not significant. The Centers for Disease Control admitted that none of these
adverse outcomes was documented to be a direct sequela of Lyme disease. These
adverse outcomes are only possible associations of Borrelia burgdorferi
maternal infection (Table 23-1).

Table 23-1 Adverse pregnancy outcomes with possible association to Lyme disease
Congenital anomlies (especially heart, great vessels)
Congenital cortical blindness
Miscarriage
Small for gestational age
Stillbirth
Toxemia

According to Mikkelsen and Palle, (ref 6) to avoid a potential adverse effect
on the fetus, the mother should be treated aggressively. Treatment is guided by
the clinical manifestations of the disease (Table 23-2).

Table 23-2
Treatment of Lyme disease during pregnancy
Disease stage Antibiotic regimen
Uncomplicated erythema migrans after first trimester:
Amoxicillin 500 mg P0 tid-qid x 21-30 days
Erythromycin 250 mg P0 qid x 21-30 days
[Newer macrolides such as Azithromycin may prove to he superior to
erythromycin]
Avoid tetracyclines, probenecid

Disseminated or late disease; first trimester infection
Intravenous antibiotics for 2-4 weeks
Ceftriaxone 2g
Penicillin G 20 million U qd

Lyme disease limited to the skin can probably be treated with amoxicillin or
erythromycin (see Chapter 18 for a different approach). Probenecid should not
be used, and the tetracyclines should be avoided. Disseminated disease, and
infections in the first trimester, should be treated with parenteral
antibiotics (ceftriaxone or penicillin – ref 6).

In 1987, Mikkelsen and Palle (ref 6) reported the case of a 29-year-old woman
who during her 24th week was bitten by a tick. She developed EM without any
systemic manifestations, with a positive antibody titer. She was treated with
penicillin for 10
days and subsequntly delivered a term baby. Histologic study of the placenta
was negative, and the antibody titer in cord and maternal blood was not
elevated.

SUMMARY
A body of evidence (ref 3 and 4) suggests that the causative agent of Lyme
disease, B. burgdorfen, can cross the placenta and infect the fetus. There are
also several reports that suggest that this may be associated with a poor fetal
outcome. However, the majority of studies have not been able to identify B.
burgdorferi as a direct cause of spontaneous abortions, congenital anomalies,
or neurologic sequelae in infants.
It is essential to realize that in the pregnant woman Lyme disease is a
clinical diagnosis regardless of her serologic status. Because the precise risk
to the fetus from an infected pregnant female is not yet clear, it is important
to be aggressive in the diagnosis and management of Lyme disease. This is
important not only for the fetus, but also for the mother. The mother is
certainly at risk for serious and potentially debilitating manifestations of
Lyme disease including arthritis, carditis, and neurologic problems.
In conclusion, Lyme disease in pregnancy is a clinical diagnosis irrespective
of serologic status.

The diagnosis must be made promptly, and treatment must be instituted in the
interest of maternal, in addition to fetal, welfare.

REFERENCES
1. Centers for Disease Control, MMWR 40(25):417, 1991.
2. Dlesk A et al: Lyme seropositivity and pregnancy outcome in the absence
of symptoms of Lyme disease, Arthritis Rheum 32(suppl):S46, 1989.
3. MacDonald AB: Human fetal borreliosis, toxemia of pregnancy, and fetal
death, Zentralbi Bakieriol Mikrobiol Hyg
[A] 263:189, 1986.
4. MacDonald AB: Gestational Lyme borreliosis, Rheum Dis Clin North Am
15(4):657, 1989.
5. Markowitt LE et al: Lyme disease during pregnancy. JAMA
255(24):3394, 1986.
6. Mikketsen AL, Palle C: Lyme disease during pregnancy. Acta Obstet
Gynecol Scand 66:477, 1987.
7. Nadal D et al: Infants born to mothers with antibodies against Borellia
burgdorferi at delivery, Eur J Pedjair
148:426, 1989.
8. Schlessinger PA et al: Maternal-fetal transmission of Lyme disease
spirochete Borrelia burgdoDferi, Ann Intern Med
103:67, 1985.
9. Sigal LH: Summary of the Fourth International Symposium on Lyme
Borreliosis, Arthritis Rheum 34(3):367, 1991.
10. Steere AG: Lyme disease, N Engi J Med 321:586, 1989.
11. Steere AC, Malawista SE: Cases of Lyme disease in the United States:
locations correlated with distribution of Ixodes dammini, Ann Intern Med
91:730, 1979.
12. Steere AC et al: The clinical spectrum and treatment of Lyme disease,
Yale J Biol Med 57:453, 1984.