The Pediatric Infectious Disease Journal Publish Ahead of Print

DOI: 10.1097/INF.0000000000001842

Early Childhood Neurodevelopmental Outcomes in Infants Exposed to Infectious Syphilis

In Utero

Valsan P. Verghese, MD1, Leonora Hendson, MBBCh, MSc2, Ameeta Singh, BMBS,

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MSc3,4, Tamara Guenette, BScN4, Jennifer Gratrix, MSc5, and Joan L. Robinson, MD3
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Department of Pediatrics, Christian Medical College, Vellore, India.

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2
Department of Pediatrics, University of Calgary, Calgary, AB.
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University of Alberta, Edmonton, Alberta
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Alberta Health Services- Edmonton STI Clinic
5
Alberta Health Services- Centralized STI Services
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Conflicts of Interest and Source of Funding: None of the authors has a conflict of interest

related to publication of this manuscript. No funding was received for this project.

Reprints are not available.

Abbreviated Title: Neurodevelopmental Outcomes in Congenital Syphilis

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Running Head: Neurodevelopmental Outcomes with Syphilis

Corresponding Author: Joan Robinson, MD

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3-556 ECHA 11405-87 Ave, Edmonton AB Canada T6G 1C9

Phone: 780-248-5540; FAX: 1- 888-790-1176; mail: jr3@ualberta.ca

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Acknowledgement: We thank Jill T. Tomlinson, CHIM, data information analyst, Neonatal and

Infant Follow-up Clinic, Glenrose Rehabilitation Hospital for collating the neurodevelopmental

outcomes for this study.

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 Abstract

Background: There are minimal neurodevelopmental follow-up data for infants exposed to

syphilis in-utero.

Methods: This is an inception cohort study of infants exposed to syphilis in utero. We reviewed

women with reactive syphilis serology in pregnancy or at delivery in Edmonton (Canada), 2002

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through 2010 and describe the neurodevelopmental outcomes of children with and without

congenital syphilis.

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Results: There were 39 births to women with reactive syphilis serology, 9 of whom had late

latent syphilis (n=4), stillbirths (n=2) or early neonatal deaths (n=3), leaving 30 survivors of

which 11 with and 7 without congenital syphilis had neurodevelopmental assessment. Those

with congenital syphilis were all born to women with inadequate syphilis treatment prior to
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delivery. Neurodevelopmental impairment was documented in 3 of 11 (27%) infants with

congenital syphilis and 1 of 7 (14%) without congenital syphilis with speech language delays in

4 of 11 (36%) with congenital syphilis and 3 of 7 (42%) without congenital syphilis.

Conclusions: Infants born to mothers with reactive syphilis serology during pregnancy are at
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high risk for neurodevelopmental impairment, whether or not they have congenital syphilis, so

should all be offered neurodevelopmental assessments and early referral for services as required.
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Keywords: congenital syphilis; neurodevelopmental outcomes; pregnancy

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 Introduction

After several years of declining trends, the incidence of congenital syphilis has seen an

increase in North America. Population rates of infectious syphilis in Canada were 0.4 to 0.6 per

100,000 population from 1993 to 20001, and steadily increased, from 0.9 in 2000 to 5.8 in 2012.2

These rates are comparable to other countries with a similar socio-economic and ethno-cultural

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background.3 In Alberta, the first case of congenital syphilis was reported in 2002 after a gap of

over 10 years.4 More than half of the nation’s early congenital syphilis from 2002 to 2011 was

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reported from Alberta.3 The majority of infants with congenital syphilis were born to indigenous

women, a significant proportion of whom did not access antenatal care despite universal

coverage for health care services.4

Syphilis can affect the central nervous system, resulting in neurologic and
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neurodevelopmental sequelae but published data on the neurodevelopmental outcomes of

exposure to syphilis in-utero and of congenital syphilis are limited. Mothers affected by syphilis

commonly have socioeconomic and other health challenges which may also impact

neurodevelopmental outcomes.5 Children with neurodevelopmental deficits may benefit from

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rehabilitation and early intervention if developmental delays or disabilities are detected.6

The objective of this study was to report on neurodevelopmental outcomes in early

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childhood for children born to mothers with infectious syphilis during pregnancy in the modern

era.
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Methods

This is a convenience inception cohort study of infants exposed to syphilis in utero. The

study protocol was approved by Health Research Ethics Board of the University of Alberta.

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 Inclusion criteria

Children born in the Edmonton zone (population 1,295,164 in 2014) to women with

reactive syphilis serology in pregnancy or in the early post-partum period in 2002 through 2010

were eligible for the study. Women with positive syphilis serology during pregnancy or in the

immediate post-partum period can be identified from the provincial Sexually Transmitted

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Infection (STI) database. The syphilis is staged as primary, secondary, early latent or late latent

disease using Alberta case definitions for syphilis (Alberta Health. Public Health Notifiable

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Disease Management Guidelines: Syphilis, 2012. Available at:

https://open.alberta.ca/publications/syphilis#summary (Accessed June 23, 2017). All cases are

reviewed, staged and managed by designated STI medical consultants.. Prior to September,

2007, individuals were screened for syphilis with a Rapid Plasma Reagin (RPR) (Macro-Vue™
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RPR kit, Becton Dickinson Microbiology Systems, Ontario, Canada) with or without a

Treponema pallidum particle agglutination (TPPA) and/or fluorescent treponemal antibody

adsorbed (FTA-ABS). On September 1st, 2007, a reverse sequence syphilis screening algorithm

was introduced province-wide with the initial syphilis serologic screen with a syphilis enzyme
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immunoassay (EIA) (Architect Syphilis TP Chemiluminescent Microparticle Immunoassay,

Abbott Laboratories, Illinois, U.S.A.). A positive EIA is followed by a quantitative RPR and a
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second or supplementary treponemal test with a syphilis INNO-LIA (INNO-LIA Syphilis,

Innogenetics NV, Ghent, Belgium). Those born to women staged as having late latent syphilis
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were excluded as perinatal late stage infection with syphilis is not thought to be a significant risk

for congenital syphilis unless there is reinfection during pregnancy. Adequate treatment for

syphilis was defined as a four-fold drop in non-treponemal titers six months post-treatment or

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 prior to conception. Congenital syphilis was defined as confirmed (detection of spirochetes by

any method or reactive serology with clinical, laboratory or radiographic evidence of disease) or

probable (reactive serology in an infant/child without clinical, nor laboratory, nor radiographic

evidence of congenital syphilis whose mother had untreated or inadequately treated syphilis at

delivery).7

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Study procedures

Charts/databases from the Alberta Health Services (AHS) Edmonton STI Clinic, the

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Royal Alexandra Hospital, and the University of Alberta Hospital were reviewed to determine

the pregnancy outcome. Maternal demographic data, gestational age and stage of syphilis at

diagnosis, maternal syphilis treatment details and infant birth data, neonatal course, and syphilis

treatment details were collected for all infants eligible for the study.
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All children exposed to syphilis in-utero are eligible for neurodevelopmental assessment

at the Neonatal and Infant Follow-up Clinic at the Glenrose Rehabilitation Hospital in

Edmonton. For this study, most of the children with and without congenital syphilis have

standardized neurodevelopmental assessments available at 18 months corrected gestational age.

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If concerns are identified at the 18 month visit or if the family has ongoing concerns, the child is

reviewed again at 36 months. Children are referred to community resources and rehabilitation as
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needed.

The neurodevelopmental assessment includes i) examination by a pediatrician

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experienced in neurodevelopmental follow-up, ii) standardized motor examination by a

physiotherapist, occupational therapist and physiatrist to detect evidence of cerebral palsy,8 iii)

visual assessment by an ophthalmologist for visual impairment, defined as corrected visual

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 acuity in the better eye worse than 20/60, and iv) hearing assessment by an audiologist for

hearing impairment defined as binaural or bilateral sensorineural hearing loss greater than 40 dB

at any frequency from 250 to 4000 Hz. At 18 months corrected age, certified

psychologists/psychometrists administer either the Bayley Scales of Infant Development II9

which yields a Mental Developmental Index (MDI) score or the Bayley Scales of Toddler and

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Infant Development10 which yields a cognitive score. At 36 months of age,

psychologists/psychometrists administer the Wechsler Preschool and Primary Scale of

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Intelligence (WPPSI-III) 11 yielding a Full Scale Intelligence Quotient (FSIQ). For

MDI/cognitive score/FSIQ the mean is 100 and the standard deviation (SD) is 15 so a score

lower than 70 (2 SD below the mean) indicates mental delay. A seizure disorder is diagnosed in

any child with clinical seizures requiring ongoing anti-epileptic treatment at the time of
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assessment. A neurodevelopmental impairment is defined as one or more of cerebral palsy,

visual impairment, sensorineural hearing loss, mental delay, or seizure disorder.12 If there is

parental report or clinical suspicion of speech language delay, this is confirmed by assessment by

speech language therapist and administration of the Preschool Language Scale – Fourth edition
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(PLS-4).13 A total language score lower than 70 (2SD below the mean) indicates speech delay.

Results
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There were 39 births (35 singletons and 2 pairs of twins) to 37 mothers with reactive

syphilis serology during the study period. Four births were excluded as the mothers had late
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latent syphilis. Two stillbirths occurred at 22 and 25 weeks gestation to women with early latent

syphilis and no prenatal care. There were three early neonatal deaths with extreme prematurity.

The first was born at 26 weeks gestation, birth weight 860g, to a mother diagnosed with early

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 latent syphilis at delivery (maternal RPR 1:128). This baby had hepatosplenomegaly and died

within hours of birth. The others were twins born at 25 weeks gestation to a mother treated for

primary syphilis one week prior to delivery (infant RPR 1:8 for both). The first twin, birth weight

730g, had hepatosplenomegaly and rash, and the second twin, birth weight 440g, had

hepatomegaly and abnormal CSF (800 leucocytes, protein 7.74 gms/L, glucose < 1.1 mmol/L,

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CSF VDRL reactive). Both twins died 8 to 10 hours after birth.

Ten of the remaining 30 infants were born to mothers adequately treated prior to

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conception for primary (n=5), secondary (n=1) and early latent syphilis (n=4). None of these 10

infants had stigmata of congenital syphilis, thrombocytopenia, elevated liver enzymes or bony

abnormalities and all were classified as having “no congenital syphilis”. The other 20 infants

were born to mothers diagnosed with primary (n=11), secondary (n=2) and early latent syphilis
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(n=7) during the current pregnancy. None of the mothers fulfilled the criteria for adequate

treatment prior to delivery and only 6 of the women were treated prior to delivery. The 20 infants

were classified as having confirmed (n=17) and probable congenital syphilis (n=3). All women

with infectious syphilis (primary, secondary and early latent syphilis) were treated with two
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doses of Benzathine penicillin G long acting 2.4. mu im given one week apart except one with

penicillin allergy who received doxycycline in the post-natal period. Treatment data were
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available for 18 of 20 infants with congenital syphilis and 7 of 10 without; all of the former

group and 2 of the latter group were treated with daily procaine penicillin for 10 days with the
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exception of one infant treated for 14 days. All were treated at birth except three asymptomatic

infants born to mothers who had tested negative in the first trimester and were later found to be

positive on post-natal testing at 2 weeks, 6 weeks and 8 months after delivery. The first of these

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 had no disability at formal neurodevelopmental assessment done after 18 months of age, while

the latter two did not come for follow up.

Seven of 10 infants with no congenital syphilis and eleven of 20 infants (9 with

confirmed and 2 with probable congenital syphilis) were available for neurodevelopmental

assessment at the NIFUC . Families of the 12 infants who did not come for follow-up had

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moved, declined follow-up, or were not contactable.

Maternal and neonatal characteristics are shown in Table 1; there were no significant

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differences in gestational age, birth weight, and those born preterm in children available for

follow-up assessment versus those not available. Prematurity rate was 5 of 10 (50%) for women

with adequate treatment prior to delivery versus 12 of 20 (60%) for those without. Abnormalities

detected in the newborn period in the infants with congenital syphilis are depicted in Figure 1
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(data are missing for 2 cases).

Lumbar punctures performed in 17 of the 18 with available treatment data showed

abnormal CSF in 10, with elevated CSF protein in all 10, CSF pleiocytosis in 8 and reactive CSF

syphilis serology in 7 (this was only performed in 8 of the 10, yielding positive VDRL in 1,
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positive FTA in 4, positive TPPA and VDRL in one and positive FTA and VDRL in one).

Results of auditory brainstem responses (ABR) in the newborn period were available in
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10 of 20 infants with “congenital syphilis” and 4 of 10 with “no congenital syphilis” and all were

normal. There was no evidence of syphilitic chorioretinitis documented in any of the infants.
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Other complications included respiratory distress syndrome (RDS) (n=5), patent ductus

arteriosus (n=4), intraventricular hemorrhage (n=2), and retinopathy (n=2 in infants born at 26

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 and 32 weeks GA). All were in infants with congenital syphilis except for RDS in one infant

with no congenital syphilis.

Neurodevelopmental outcomes

Eleven children with congenital syphilis and 7 with no congenital syphilis had their initial

standardized neurodevelopmental assessment at a mean age of 19 months (range 17 to 25

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months). Five with congenital syphilis and one with no congenital syphilis had repeat

neurodevelopmental assessment at a mean age of 35 months (range 31 to 38 months) for ongoing

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clinical concerns. Neurodevelopmental outcomes are summarized in Table 2.

Amongst children with congenital syphilis, 3 (27%) had a disability. One had a vitreous

hemorrhage, retinal detachment leading to unilateral blindness and Hutchinson’s teeth. The

second child had microcephaly, mental delay and seizure disorder and the third had isolated
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mental delay. The first two also had speech delay as did another child with isolated speech delay.

In the “no congenital syphilis” cases, one child had a disability (mental delay with speech

language delay) and two other children had isolated speech delay.

Discussion
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This is a novel study with standardized assessment of neurodevelopmental outcomes in

infants born to mothers with reactive syphilis serology during pregnancy. A high incidence of
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stillbirths and preterm deliveries in women with syphilis during pregnancy has been previously

documented in Alberta14 and in a previous study from Brazil.15 As would be expected in the
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absence of re-infection, we observed no infants with congenital syphilis born to mothers who

were adequately treated prior to conception. Baseline characteristics did not differ markedly

between infants with and without congenital syphilis but the overall prematurity rate was

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 strikingly high at 57%. A high proportion of mothers were indigenous (68% with data available);

indigenous persons represent about 3.8% of Canada’s total population but sexually transmitted

infection (STI) prevalence in indigenous people is higher than that of the overall population.16,17

The reasons for this are not clear but a recent First Nations Regional Health Survey stressed the

importance of colonial history, barriers to health care services and socio-economic disadvantage.

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Clinical manifestations of hepatomegaly and splenomegaly were found at birth in about

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one third of infants with confirmed congenital syphilis, followed in frequency by hydrops and

rash. The most frequent laboratory abnormality was an abnormal CSF while bone lesions were

uncommon, as noted in previous studies.18,19 No infant had sensorineural hearing loss but two

had retinopathy (of which one case may have been due to prematurity) and one had retinal
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detachment.

Although intellectual disability has been documented as a sequela of congenital syphilis20

with rates of approximately 25% quoted in the literature21, data on neurodevelopmental

assessment of infants with congenital syphilis is sparse. The only other study from the modern
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era that we identified documented sequelae in 16 infants at 8 to 51 months of age including

developmental delay in 14 (87.5%) as well as other sequelae such as microcephaly, cortical

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atrophy, seizures, and paresis.15 However, formal developmental and neuro-sensory assessment

or IQ scores were not documented in these children.

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The current study demonstrated a high incidence of neurodevelopmental impairment in

the children with and without congenital syphilis. The presence of disability including low IQ

scores and speech delay in spite of no sensorineural hearing loss presumably reflects the

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 similarities in demographic and behavioral factors between mothers who had been adequately

treated for syphilis and those inadequately treated, including predominantly vulnerable social

circumstances, substance use, young age and multiparity. Confounding factors include other co-

morbidities known to cause neurodevelopmental delay, in particular low birth weight and

prematurity, 22fetal alcohol spectrum disorder, 23and exposure to other substances antenatally.24

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The trend towards increased disability at the 36-month follow up visit compared to the

18-month visit suggest that children born to mothers with infectious syphilis during pregnancy or

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at the time of delivery should be followed up into late childhood for identification and treatment

of developmental problems that may become more evident as they get older.

A limitation of our study is the small numbers of children in each group, which in part

reflects the fact that this vulnerable population had poor healthcare-seeking behavior not just for
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themselves but also for their children with regards to regular follow up. This is reflected in the

fact that only two of eleven with congenital syphilis and three of the seven without congenital

syphilis were living with their biologic parents or extended family at follow up. A larger sample

may have shown significant differences between those with and without congenital syphilis.
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Another limitation is our strict definition of adequate treatment of syphilis during pregnancy

(four-fold drop in non-treponemal titers six months post-treatment) as there is often inadequate
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time following treatment during pregnancy to achieve these serologic criteria; it is possible that

the 3 children that we diagnosed as having probable congenital syphilis were not infected. Other
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limitations include a lack of neuro-imaging to support and explain neurodevelopmental

outcomes, and lack of follow-up beyond early childhood. Finally, had our study methods and

funding allowed, we would have compared the neurodevelopmental outcomes in a group of

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 control children from the same socioeconomic group with no exposure to syphilis to determine

the contribution of syphilis exposure to poor outcomes.

In conclusion, this study supports the need for formal neurodevelopmental follow-up for

all infants born to women with primary, secondary or early latent syphilis during pregnancy,

even in the absence of congenital syphilis. Ideally additional follow up studies should be

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conducted in infants with congenital syphilis and compared to a larger control group of infants to

further delineate the frequency and types of adverse neurodevelopmental outcomes.

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 References

1. Public Health Agency of Canada. Report on sexually transmitted infections in

Canada: 2008. Available at: http://www.phac-aspc.gc.ca/std-mts/report/sti-

its2008/PDF/10-047-STI_report_eng-r1.pdf. Accessed 23 November 2016.

2. Totten S, MacLean R, Payne E. Infectious Syphilis in Canada 2003-2012.Canada

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Communicable Diseases Report Vol 41-02, Feb 5, 2015. Available at:

http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/15vol41/dr-rm41-

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02/assets/pdf/15vol41_02-eng.pdf Accessed 20 December 2016..

3. Public Health Agency of Canada. Report on Sexually Transmitted Infections in

Canada: 2011. Published July 2014. Available at:

http://www.catie.ca/sites/default/files/64-02-14-1200-STI-Report-2011_EN-
EP
FINAL.pdf. Accessed 23 November 2016.

4. Singh AE, Sutherland K, Lee B, Robinson JL, Wong T. Resurgence of early

congenital syphilis in Alberta. Can Med Assoc J . 2007; 177: 33-36.

5. Ricci JM, Fojaco RM, O’Sullivan MJ. Congenital syphilis: The University of
C

Miami/Jackson Memorial Medical Center experience, 1986-1988. Obstet Gynecol.

1989; 74 :687-693.
C

6. American Academy of Pediatrics. Identifying infants and young children with

developmental disorders in the Medical Home: An algorithm for developmental

A

surveillance and screening. Pediatrics. 2006;118 :405-420.

7. Alberta Health Public Health Notifiable Disease Guidelines. Congenital Syphilis.

https://open.alberta.ca/dataset/e341ccf6-c0dc-45aa-9b4c-

13

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
 2e7b53769340/resource/29aeea4c-2903-4bff-8c3d-

e577851398e6/download/Guidelines-Congential-Syphilis-2012.pdf Accessed 6 July

2017

8. Bax, M. C. Terminology and Classification of Cerebral Palsy. Dev Med Child Neurol.

1964; 11: 295-297.

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9. Bayley N. Bayley Scales of Infant DevelopmentTM - Second Edition. San Antonio,

TX: Harcourt Assessment, Inc.; 1993.

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10. Bayley N. Bayley Scales of Infant and Toddler DevelopmentTM - Third Edition. San

Antonio, TX: Harcourt Assessment, Inc.; 2006.

11. Wechsler D. Wechsler Preschool and Primary Scale of Intelligence - Third Edition.

San Antonio, TX: The Psychological Corporation; 2002.

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12. Synnes A, Luu TM, Moddemann D, Church P, Lee D, Vincer M, Ballantyne M,

Majnemer A, Creighton D, Yang J, Sauve R. Determinants of developmental

outcomes in a very preterm Canadian cohort. Arch Dis Child Fetal Neo Edition. 2017

May 1;102(3):F235-4.
C

13. Zimmerman IL, Steiner VG, Pond RE. Preschool Language Scale (PLS-4): 4th ed.

San Antonio, TX: Pearson; 2002

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14. Caddy SC, Lee BE, Sutherland K, Robinson JL, Plitt SS, Read R, Singh AE.

Pregnancy and neonatal outcomes of women with reactive syphilis serology in

A

Alberta, 2002-2006. J Obstet Gynaecol Can. 2011; 33: 453-459.

15. Lago EG, Vaccari A, Fiori RM. Clinical features and follow-up of congenital

syphilis. Sex Transm Dis. 2013; 40:85-94.

14

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
 16. First Nations Information Governance Centre (FNIGC). (2012). First Nations

Regional Health Survey (RHS) 2008/10: National report on Adults, Youth and

Children living in First Nations Communities. (Ottawa: First Nations Information

Governance Centre [FNIGC]). Available at:

http://fnigc.ca/sites/default/files/First_Nations_Regional_Health_Survey_2008-

D
10_National_Report.pdf (Accessed November 29, 2016).

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17. Public Health Agency of Canada. (2010). Population-Specific HIV/AIDS Status

Report: Aboriginal Peoples. (Ottawa: Public Health Agency of Canada). Available at:

http://www.catie.ca/sites/default/files/26344.pdf (Accessed November 29, 2016).

18. Bitnun A, Lee E, Jones F, Ryan G. Chapter 52: Implications of the fetus of maternal
EP
infections in pregnancy. In Cohen and Powderly: Infectious Diseases, 3rd Edition,

2010. Pub: Mosby.

19. Robinson JL; Canadian Paediatric Society, Infectious Diseases and Immunization

Committee. Congenital syphilis: No longer just of historical interest. Paediatr Child

C

Health. 2009; 14: 337.

20. Berg JM, Kirman JH. Syphilis as a cause of mental deficiency. Br Med J. 1959;
C

2(5149): 400–404.

21. Brosco JP, Mattingly M, Sanders LM. Impact of specific medical interventions on
A

reducing the prevalence of mental retardation. Arch Pediatr Adolesc Med. 2006; 160:

302-309.

15

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
 22. Vohr B, Wright LL, Hack M, Aylward G, Hirtz D. Follow-up Care of High-Risk

Infants. Pediatrics. 2004;114:1377–1397.

23. Godel J; First Nations and Inuit Health Committee, Canadian Pediatric Society. Fetal

alcohol syndrome. Paediatr Child Health. 2002;7:161-174.

24. Messinger DS, Bauer CR, Das A, Seifer R, Lester BM, Lagasse LL, et al. the

D
maternal lifestyle study: cognitive, motor and behavioral outcomes of cocaine-

exposed and opiate-exposed infants through three years of age. Pediatrics.

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2004;113:16–20.
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A

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 Figure Legends

Figure. Baseline characteristics of infants with congenital syphilis (N=18)

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Table 1. Baseline characteristics of infants born to mothers with reactive syphilis serology during pregnancy

Maternal characteristics
Congenital syphilis – No congenital syphilis – Congenital syphilis – No congenital syphilis – no
follow-up available (n= follow-up available (n=7) no follow-up (n=9) follow-up (n=3)

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11)
Median Maternal Age (IQR) 26 (20-31) 29 (22-36) 26 (17-39) 28 (18-34)
Indigenous ethnicity (First 9 (81.8%) 4 (57.1%) 4 (44.4%) 1 (33.3%)
Nations, Metis and Inuit)
Maternal substance use 10 (90.9%)1 5 (71.4%)2 6 (66.7%)3 2 (66.6%)4
5
Maternal HCV +ve 5 (45.5%) 5 (71.4%) 1 (11.1%) 0
Maternal gravidity, mean ± 4 (± 2) 6 (±3) 4 (± 3)6 5 (± 3)
SD
Vaginal delivery 7 (63.6%) 5 (71.4%) 8 (89%) 1 (33.3%)

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Time of maternal treatment for syphilis
Preconception 0 7 (100%) 0 1 (33.3%)
Prenatal 3 (27.3%) 0 3 (33.3%) 2 (66.7%)
Postnatal 8 (72.7%) 0 6 (66.7%) 0
Neonatal characteristics
Median gestational age at
35 (29-36) 37 (33-39) 38 (31-41) 36 (32-40)
birth in weeks (IQR)
Preterm <37 weeks 9 (81.8%) 3 (42.9%) 3 (33.3%) 2 (66.6%)
Median birth weight in kg 3.1 (1.5-3.7)7
2.0 (1.5-3.1) 2.8 (1.7-3.1) 3.3 (1.6-3.9)
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(IQR)
1 min Apgar, mean ± SD
5 (± 3) 5 (± 4) 6 (± 3)8 7 (± 2)

5 min Apgar, mean ± SD

7 (± 2) 8 (± 2) 7 (± 3)9 8 (± 1)
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1
tobacco (n=8), alcohol (n=8), cocaine (n=8), marijuana (n=5), intravenous drugs (n=2)
2
tobacco (n=4), alcohol (n=3), cocaine (n=2), methadone (n=2), street drugs (n=1)
3
tobacco (n=3), alcohol (n=3), cocaine (n=4), marijuana (n=1)

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 D
4
cocaine (n=2), tobacco (n=1), alcohol (n=1), marijuana (n=1), intravenous drugs (n=1).
5
No children have HCV infection.
6
Data available for only 8 children
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Data available for only 8 children
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Data available for only 8 children

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9
Data available for only 8 children

Legend: IQR- interquartile range; NIFUC – Neonatal and Infant Follow-up Clinic; SD – standard deviation

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 Table 2. Neurodevelopmental outcomes in infants born to mothers with reactive syphilis
serology

Congenital syphilis No congenital

(n=11) syphilis (n=7)
Any neurodevelopmental 3 (27.3) 1 (14.3)
impairment, n (%) 1
Mental delay, FSIQ < 70a, n (%) 2 (18.2) 1 (14.3)
Vision loss, n (%) 1 (9.0) 0
Seizure disorder + microcephaly, 1 (9.0) 0

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n (%)
Other diagnoses:
Speech language delay 4 (36.4) 3 (42.9)

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1
Any neurodevelopmental impairment was defined as one or more of cerebral palsy, visual
impairment, sensorineural hearing loss, mental delay, or seizure disorder.
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 Figure. Baseline characteristics of infants with congenital syphilis (n=18)*

80%

60%

40%

D
20%

0%

TE
* Long bone Xrays and CSF analysis performed in only 17
EP
infants, and ALT in 12 infants.

Legend: ALT - alanine transaminase

C
C
A

21

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.