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Epidemiology
Original Article
Probability of vertical transmission of Chlamydia trachomatis estimated from national registry data
  1. Minna Honkila1,2,
  2. Erika Wikström2,
  3. Marjo Renko1,2,
  4. Heljä-Marja Surcel3,
  5. Tytti Pokka1,2,
  6. Irma Ikäheimo4,
  7. Matti Uhari1,2,
  8. Terhi Tapiainen1,2
  1. 1 Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
  2. 2 PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland
  3. 3 National Institute for Health and Welfare, Oulu, Finland
  4. 4 Nordlab Oulu, Oulu University Hospital, Oulu, Finland
  1. Correspondence to Dr Minna Honkila, Department of Children and Adolescents, Oulu University Hospital, P.O. Box 23, OYS, Oulu FIN-90029, Finland; minna.honkila{at}ppshp.fi

Abstract

Objectives Chlamydia trachomatis colonisation is common in pregnant women, and it has been claimed that mother-to-child transmission may occur in 10%–70% of deliveries. C. trachomatis infections are nevertheless rarely encountered in infants in clinical practice. In order to evaluate the reason for this discrepancy, we designed a nationwide study of the C. trachomatis vertical transmission.

Methods Children with a possible C. trachomatis infection were identified from two national health registries in 1996–2011. Copies of the children's medical records were reviewed and maternal serum bank samples obtained during the index pregnancies were analysed for C. trachomatis antibodies. The risk of vertical transmission was calculated using data from two earlier studies in which nucleic acid amplification test (NAAT) positivity and seroconversion rates among women in the general population were reported.

Results Altogether 206 children had a possible C. trachomatis infection, which represents 0.22 per 1000 live births (95% CI 0.19 to 0.25). The risk of vertical transmission among the estimated 24 901 NAAT-positive mothers was 0.8% (95% CI 0.7 to 0.9). Based on the annual seroconversion rate of maternal antitrachomatis antibodies, the risk of vertical transmission was 1.8% (95% CI 1.5 to 2.0). Altogether 35% of the maternal serum samples obtained in the first trimester of a pregnancy leading to a C. trachomatis infection in the infant were negative, implying that the infection was acquired during pregnancy.

Conclusions C. trachomatis infections in infants were rare, with a population-based occurrence of 0.22 per 1000 live births. The risk of vertical transmission of C. trachomatis in the population was <2%, which is significantly lower than reported earlier.

  • CHLAMYDIA TRACHOMATIS
  • CHILDREN
  • EPIDEMIOLOGY (CLINICAL)
  • SEROLOGY

https://doi.org/10.1136/sextrans-2016-052884

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    Introduction

    Vertical transmission rate of Chlamydia trachomatis during delivery to the infants of culture-positive mothers has varied markedly in previous studies,1–5 and little is known about vertical transmission rate from nucleic acid amplification test (NAAT)-positive mothers,6 (table 1).

    View this table:
    Table 1

    Previous studies of Chlamydia trachomatis infections in mothers during pregnancy or post partum and the outcome for their infants

    About 2.7% of pregnant women in Finland have been found to be carriers of C. trachomatis on the basis of NAAT positivity in first-void urine.7 The recent Red Book (2015 Report of the Committee on Infectious Diseases, American Academy of Pediatrics) states that the prevalence of C. trachomatis positivity among young adult American females is 3.3%, acquisition of C. trachomatis occurs in 50% of vaginally delivered infants and 25%–50% of those who contract C. trachomatis at birth are at risk of developing the clinical disease.8

    Despite the fact that genital chlamydial nucleic acid is frequently detected in women of reproductive age,7 our clinical experience is that we rarely see and diagnose infants with C. trachomatis infections. Universal screening for C. trachomatis during pregnancy is not performed in our country, and >99% of the infants attend regular mother and baby clinics during the first year of life. In order to understand better the vertical transmission and epidemiology of C. trachomatis infections, we systematically collected data on C. trachomatis infections in a nationwide survey using comprehensive national health registries and reviewed the medical records of each possible case. We aimed to calculate a reliable estimate for the risk of vertical transmission in an unselected population-based research setting. In addition, we measured C. trachomatis antibodies from maternal serum bank samples obtained during the index pregnancies in order to estimate the likely timing of the acquisition of maternal C. trachomatis infections leading to an infected infant.

    Patients and methods

    We performed a population-based nationwide cohort study of the C. trachomatis vertical transmission. There were 933 823 children born in Finland from 922 263 deliveries during the 16-year study period from 1 January 1996 to 31 December 2011.9 Children with a possible C. trachomatis infection in the age group 0–4 years were identified from two Finnish national health registries, the National Infectious Diseases Register (NIDR) and the Care Register for Health Care, from 1 January 1996 to 31 December 2011. The age group of 0–4 years was chosen as it is the youngest age group used in the NIDR for data retrieval. We obtained the copies of all the medical records of children with a possible C. trachomatis infection from health centres, mother and baby clinics and hospitals in order to validate the registry data and linked them with their mothers using the national Medical Birth Register. We then obtained the mothers' serum samples drawn during the first trimester of the index pregnancy from the Finnish Maternity Cohort (FMC) serum bank and measured their C. trachomatis serology. In addition, we collected data on the mothers' C. trachomatis infections from the NIDR. Universal screening of pregnant women for C. trachomatis was not performed during that period, nor was antimicrobial prophylaxis provided for newborn infants. The protocol was found ethically acceptable by both the Review Board of the National Institute for Health and Welfare, Helsinki, Finland (THL/187/5.05.00/2012) and the Regional Ethics Committee of the Northern Ostrobothnia Hospital District, Oulu, Finland (EETTMK 63/2010).

    National Infectious Diseases Register

    Surveillance of C. trachomatis infections in Finland is based on mandatory notifications made in accordance with the Communicable Diseases Act and Decree of 1987. Between 1987 and 1997, physicians reported confirmed C. trachomatis-positive cases to the NIDR, and from 1997 onwards laboratories have been responsible for the notifications. Each laboratory notification includes the patient's personal identity number, gender and age and the sampling site and test method used. The incidence rate of C. trachomatis infection based on the reported figures to the NIDR was 374 (95% CI 365 to 383)/10 000 person-years at risk (PYR) in women aged under 23 years and 70 (95% CI 66 to 75)/10 000 PYR in women aged between 23 and 28 years in Finland in 2001–2003.10 No data on the treatment provided or its efficacy are reported to the NIDR.

    Care Register for Health Care

    The Care Register for Health Care (formerly known as the Hospital Discharge Register) consists of data on patients discharged from inpatient care and specialised outpatient care, and is maintained by the National Institute for Health and Welfare, Finland. The registry data include the patient's personal identity number, the reason for seeking care, diagnoses and the date of discharge. We used the International Classification of Diseases (ICD-10) codes A74* (other diseases caused by Chlamydiae), H13* (disorders of conjunctiva in diseases classified elsewhere), J16.0 (chlamydial pneumonia) and P23.1 (congenital pneumonia due to Chlamydia) to retrieve data from the Care Register for Health Care.

    FMC serum bank

    The FMC serum bank is a nationwide repository for maternal serum samples obtained during the first trimester of pregnancy that was established by the National Institute for Health and Welfare in 1983. Since then >850 000 pregnant women have given written informed consent for their serum samples, stored at −25°C, to be used for research purposes. In our survey, maternal serum samples obtained during the index pregnancies were available for 80% of the mothers with an infant infected with C. trachomatis.

    Serology

    We used the commercial enzyme immunoassay (Medac Diagnostika) to detect serum IgG antibodies to C. trachomatis from the mothers' serum samples obtained during the index pregnancies in 1996–2011 for estimation of the timing of the acquisition of the C. trachomatis infection. C. trachomatis antibodies in the maternal serum samples were measured in the laboratory of the National Institute of Health and Welfare, Finland, in 2015.

    Estimation of the risk of vertical transmission

    We calculated two scenarios for the risk of vertical transmission of C. trachomatis based on our data and two earlier studies among pregnant women in Finland. For the first scenario, we estimated the total number of chlamydia-positive mothers during the period concerned using data quoted by Kurkinen et al,7 who reported the prevalence of C. trachomatis infection in the maternity healthcare population (N=1070) in Päijät-Häme in Finland between autumn 2003 and spring 2004. Altogether, 10 out of 793 (1.3%) pregnant women were NAAT-positive for C. trachomatis based on screening during the first trimester of the pregnancy. The prevalence was 2.7% (95% CI 1.8 to 4.2) when taking into account the data from the NIDR of women who were reported to have C. trachomatis infection and were simultaneously pregnant during the study period. In order to estimate the risk of vertical transmission, we used the number of infected infants from our data as the numerator and the estimated proportion of chlamydia-positive mothers (N=24 901) as the denominator.7

    For the second scenario, we used data presented by Lyytikäinen et al,10 who studied the annual incidence rates of C. trachomatis infection among Finnish women by serology using paired serum bank samples obtained during two consecutive pregnancies. Altogether, 7999 women's serum samples were analysed for C. trachomatis IgG antibodies. A total of 161 seroconversions occurred among 6632 women who were seronegative at baseline. The seroconversion rate was 188 (95% CI 86 to 290)/10 000 PYR for those aged under 23 years and 97 (95% CI 48 to 146)/10 000 PYR among those aged 23–28 years, the average for the total population being 127/10 000 PYR. In order to estimate the risk of vertical transmission for the second scenario, we used the number of infected infants in our data as the numerator and the estimated proportion of chlamydia-positive mothers (N=11 712) as the denominator.10

    Statistical analysis

    The occurrence of possible and confirmed C. trachomatis infections was assumed to follow a Poisson distribution, and 95% CIs were calculated accordingly. The statistical analyses were performed using SPSS V.22 software (SPSS, Chicago, Illinois, USA) and StatsDirect statistical software.11

    Results

    We identified 213 children with a possible C. trachomatis infection from the national health registries: 151 from the NIDR, 38 from the Care Register for Health Care and 24 from both (figure 1). We obtained the medical records of all children with a complete personal identity number (N=163) to validate the registry data and to characterise the clinical features of C. trachomatis infections. Altogether, 135 children's medical records were available for the review. All cases found from the NIDR were confirmed. For seven children identified from the Care Register for Health Care, it was decided on the basis of the review of the medical records that they had not had a C. trachomatis infection but the primary physician had unintentionally entered the wrong ICD-10 code. These cases were excluded. Thus, there were 206 children with a C. trachomatis infection based on the validated registry data, 123 infants of whom were used to characterise the clinical features of C. trachomatis infections.

    Figure 1
    Figure 1

    Study design. ICD, International Classification of Diseases.

    Conjunctivitis was the most common clinical manifestation of C. trachomatis infection, being diagnosed in 106/123 infants (86%). One-quarter of the infants (30/123) had respiratory tract symptoms, and pneumonia was diagnosed in 19/123 infants (15%). Altogether, 49/123 infants (40%) were hospitalised on account of the C. trachomatis infection. A total of 10/123 infants (8%) received oxygen therapy and two (2%) were admitted to the intensive care unit. NAAT was the most widely used diagnostic test method for detecting the C. trachomatis infection in the 123 infants (66%), followed by antigen detection in 25%. Cell culture was used in 12% of cases and serology in 4%.

    The mean age of the 123 mothers whose infants had a confirmed C. trachomatis infection was 24 years (SD 5.3) and the majority (74%) were primigravida. All the mothers except one delivered vaginally. Altogether, 51/123 (41%) mothers had a microbiologically confirmed C. trachomatis infection at some point in their lives, but only five had tested positive for C. trachomatis during the index pregnancy (table 2).

    View this table:
    Table 2

    Chlamydia trachomatis infections in mothers whose infants had a confirmed C. trachomatis infection during the first 3 months of life (N=123)

    A serum sample obtained during the first trimester of the index pregnancy was available for 99/123 (80%) of the mothers of infants with a confirmed chlamydial infection (table 2). Altogether, 35 (35%) of them were negative for C. trachomatis-specific IgG antibodies. Of the 35 seronegative mothers, 26 (74%) had negative registry data before the index pregnancy. Nine seronegative mothers had a confirmed C. trachomatis infection before the index pregnancy and two of them were tested positive during the index pregnancy. None of the mothers was HIV-positive, but two had a hepatitis C. trachomatis infection. None of them had a hepatitis B infection or syphilis.

    The 206 children who had a possible C. trachomatis infection during the 16-year period represent an occurrence rate of 0.22 per 1000 live births (95% CI 0.19 to 0.25), while the 123 microbiologically confirmed C. trachomatis cases whose symptoms started before 3 months of age gave an occurrence rate of 0.13 per 1000 live births (95% CI 0.11 to 0.16).

    There were altogether 922 263 deliveries in Finland during the 16-year period, and we chose two scenarios for estimating the risk of vertical transmission. The resulting rates were 0.8% (95% CI 0.7 to 0.9) among the estimated 24 901 NAAT-positive mothers and 1.8% (95% CI 1.5 to 2.0) among the estimated 11 712 mothers with a newly acquired infection based on the annual seroconversion rate of antitrachomatis antibodies (table 3).

    View this table:
    Table 3

    The risk of vertical transmission for Chlamydia trachomatis (with 95% CI) delivered from the number of infants infected with C. trachomatis found in the population and C. trachomatis positivity among pregnant women

    Discussion

    We found that the population-based occurrence of C. trachomatis infections in infants was low, 0.22 per 1000 live births, and vertical transmission leading to an infected infant occurred in <2% of the pregnancies. We estimated that the risk of vertical transmission was 0.8% among women with C. trachomatis nucleic acid positivity and 1.8% among those with a newly acquired infection within the last year. Much higher estimates for vertical transmission rates have been reported among selected C. trachomatis culture-positive women, ranging from 10% to 70% for colonisation and from 10% to 30% for symptomatic infections.1–5

    Children born to culture-positive women have been shown in earlier studies,1–5 to have a higher risk of vertical transmission than those born to NAAT-positive women. This is attributable to the fact that NAATs do not require living organisms and these methods are able to detect a single copy of a bacterial nucleic acid. Thus, the most likely explanation for our low risk of vertical transmission as compared with earlier studies is that modern methods actively diagnose mothers whose chlamydial infections are not as contagious as the culture-positive infections identified in the 1970s and 1980s.1–5 In addition, we evaluated the risk of vertical transmission of C. trachomatis in an unselected population.

    An untreated C. trachomatis infection during pregnancy can lead to significant maternal and neonatal morbidity,12 ,13 and the Centers for Disease Control and Prevention recommends screening all pregnant women for chlamydial genital infection during their first prenatal visit. Repeated screening in the third trimester is recommended only if the mother has a high risk of contracting the infection. The screening of pregnant women is a standard practice in many high-income countries, but they are not yet routinely screened for chlamydial infection in Finland. In any case, our estimates for the timing of the mother's acquisition of the chlamydial infection, based on antitrachomatis antibodies obtained during the index pregnancy, show that a significant number of maternal C. trachomatis infections leading to an infected infant are acquired after the first trimester and would remain undiagnosed if screening were organised only during the first trimester. The sensitivity of C. trachomatis antibodies for recent infection is 67%–95%, that is, a lack of antitrachomatis antibody development during chlamydial infection has been demonstrated in 5%–33% of cases.5 ,14 We therefore consider that the lack of antibodies in a third of our mothers in the first trimester suggests that at least one quarter of the maternal genital chlamydial infections have occurred later in the pregnancy.

    All the mothers of infants infected with C. trachomatis in our series except one delivered vaginally. The one remaining mother delivered by an unplanned Caesarean section, but it was not reported whether the amniotic membranes had ruptured prior to the operation. This is in accordance with previous reports that the risk of perinatal transmission is much higher after vaginal delivery than after Caesarean section.15

    C. trachomatis in infants can be detected by means of various laboratory tests, that is, culture, an antigen detection test, NAAT and serology. NAAT, both from conjunctival swabs and nasopharyngeal aspirates, was the most frequently used test method in our material. This has been found to perform well with respect to sensitivity (>90%) and specificity (≥99%) relative to other tests and to detect approximately 20%–50% more C. trachomatis infections than other tests.16–17 NAAT is widely used in clinical practice, but has not been approved by the Food and Drug Administration for use with conjunctival or nasopharyngeal specimens from children.

    The strengths of our investigation are the use of nationwide data and the comprehensive nature of the national registries. It is also one of the first studies to describe the risk of vertical transmission of C. trachomatis in an unselected population. The validity of our findings is further strengthened by the opportunity to obtain maternal data from the NIDR and the ability to analyse C. trachomatis antibodies from the mothers' serum bank samples taken earlier during their pregnancies. We also reviewed the medical records of the children to validate the registry data.

    Our study has some limitations. First, we collected the data retrospectively and active prospective surveillance could have revealed additional C. trachomatis infections. The majority of the infants with a C. trachomatis infection were clearly symptomatic and many had been admitted to hospital. All in all, 99.6% of infants in Finland attend mother and baby clinics regularly, with approximately eight visits during the first year of life,18–19 and it is unlikely that primary care physicians would miss infants with severe C. trachomatis infections, although an asymptomatic C. trachomatis infection causing only minor symptoms could have escaped notice. Thus, the true incidence of C. trachomatis infections in infants might have been higher if there had been active surveillance of the infants for chlamydial infections. Second, pregnant women do not routinely undergo screening for C. trachomatis genital infections in Finland, therefore, in countries with national screening programmes the number of infants infected with C. trachomatis per 1000 births would probably be even lower than in our study. Finally, there were some missing data as maternal serum samples were available only for 99/123 (80%) mothers.

    In conclusion, C. trachomatis infections in infants were rare in our unselected national population, with an occurrence rate of 0.22 per 1000 live births. The risk of vertical transmission leading to an infected infant was <2%. Approximately one-fourth of the maternal infections leading to an infected infant occurred after the first trimester of pregnancy and would probably have been missed if chlamydial screening had been performed only during the first trimester of pregnancy.

    Key messages

    • Chlamydia trachomatis colonisation is common in pregnant women, and it has been claimed that mother-to-child transmission may occur in 10%–70% of deliveries.

    • The population-based occurrence of C. trachomatis infections in infants was 0.22 per 1000 live births (95% CI 0.19 to 0.25) in the present study.

    • The risk of vertical transmission of C. trachomatis leading to an infected infant was <2%, which is significantly lower than reported earlier.

    Acknowledgments

    This study was supported by the Alma and KA Snellman Foundation, Oulu, Finland.

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    Supplementary materials

    • Abstract in Finnish

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Footnotes

    • Handling editor Jackie A Cassell

    • Contributors MH and EW collaborated in the writing of the manuscript. MH was also involved in the design and conducting of the study. MH and TP carried out the initial analyses. MR, H-MS and II supervised data collection, critically reviewed the manuscript and approved the final manuscript as submitted. MU and TT conceptualised and designed the study, supervised data collection, critically reviewed the manuscript and approved the final manuscript as submitted. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

    • Competing interests None declared.

    • Ethics approval Review Board of the National Institute for Health and Welfare, Helsinki, Finland; Regional Ethics Committee of the Northern Ostrobothnia Hospital District, Oulu, Finland.

    • Provenance and peer review Not commissioned; externally peer reviewed.