Infections Before Pregnancy Linked to Higher Risk of Congenital Heart Disease in Babies

One of the largest studies ever conducted on pre-pregnancy health has found that infection-related exposures measured before conception are associated with a markedly elevated risk of congenital heart disease in babies. The research, published in BMC Public Health, drew on a population-based cohort of 630,968 women who were planning pregnancy in Guangdong Province, South China, between 2014 and 2018. Among their infants, 1,312 babies, or roughly 0.21 percent, were diagnosed with congenital heart disease through the regional birth defects registry. The scale of the dataset matters enormously in this field, because congenital heart disease is the most common birth defect worldwide yet remains difficult to study, since any single exposure is rare and individual studies often lack the statistical power to detect reliable associations.

The study’s central innovation lies in its timing. Most previous research on infection and heart defects has focused on infections contracted during pregnancy, particularly in the first trimester when the embryonic heart is forming. This new analysis shifts the window backward, asking whether the state of a woman’s immune system and reproductive tract before she conceives might also shape her child’s cardiac risk. The investigators assessed two broad categories of preconception exposure. The first comprised active reproductive tract infections, specifically candidiasis and Chlamydia trachomatis infection, diagnosed at the preconception examination. The second comprised immunoglobulin G seropositivity to three well-known pathogens: cytomegalovirus, Toxoplasma gondii, and rubella virus. Immunoglobulin G antibodies indicate prior exposure to a pathogen and persist in the blood for years, so seropositivity serves as a marker of a woman’s immunological history rather than of an active acute illness at the time of testing.

The data came from China’s National Free Preconception Health Examination Project, a government program that offers voluntary health screening to couples planning marriage or pregnancy. All participants provided written informed consent, and the retrospective analysis of anonymized records was approved by the Institutional Review Board of Guangdong Women and Children Hospital. Because the screening program covers a defined population rather than a selected sample of hospital patients, the cohort reflects a broad cross-section of women of reproductive age in one of China’s most populous provinces, which strengthens the generalizability of the findings within similar settings.

Statistically, the team used multivariable modified Poisson regression with robust error variance, a modeling approach widely favored in epidemiology when the outcome of interest is relatively common and researchers want to estimate relative risks directly rather than odds ratios, which can overstate risk in such settings. The models adjusted for potential confounding factors, and the authors reported both adjusted relative risks and risk differences per 1,000 births, each accompanied by 95 percent confidence intervals. The primary outcome, congenital heart disease, was ascertained from the birth defects registry, providing a standardized and population-wide mechanism for capturing diagnoses rather than relying on self-report or single-hospital records.

The results were striking across the board. Chlamydia trachomatis infection detected before conception was associated with an adjusted relative risk of 1.89, meaning the risk of congenital heart disease in offspring was nearly doubled among exposed women, with a confidence interval of 1.14 to 3.15. Even more pronounced was the association with cytomegalovirus IgG seropositivity, which carried an adjusted relative risk of 2.70, with a confidence interval of 2.26 to 3.22. Candidiasis was linked to an adjusted relative risk of 1.50, rubella IgG seropositivity to 1.59, and Toxoplasma gondii IgG seropositivity to 1.32, all with confidence intervals excluding the null value of 1. In other words, every one of the five preconception infection-related exposures examined showed a statistically significant association with elevated offspring heart defect risk in the fully adjusted models.

Perhaps the most eye-catching numbers emerged when the researchers examined women exposed to more than one factor. Among women with both Chlamydia trachomatis infection and cytomegalovirus IgG seropositivity, the adjusted relative risk reached 5.14, with a confidence interval of 2.92 to 9.06. Women with candidiasis combined with cytomegalovirus IgG seropositivity showed an adjusted relative risk of 3.72, with a confidence interval of 2.53 to 5.49. These joint-exposure estimates suggest that women carrying multiple infection-related markers before conception may face substantially higher absolute risks than those with any single marker. However, the authors are careful to frame these findings appropriately: the elevated estimates in jointly exposed groups describe joint exposure patterns and should not be interpreted as evidence of biological interaction, meaning the study cannot establish that the two exposures amplify each other’s effects at a mechanistic level.

The biological plausibility of a link between maternal infection and fetal cardiac development has a long scientific pedigree. Congenital heart disease arises from disruptions in the intricate choreography of embryonic heart formation, which occurs largely within the first eight weeks of gestation. Maternal immune activation, whether triggered by active infection or by the lingering immunological landscape left by past pathogens, is thought in some contexts to influence early embryonic environments through inflammatory signaling, altered cytokine profiles, and effects on placental development. Rubella is a classic and well-established teratogen, capable of causing a constellation of congenital defects including cardiac anomalies when infection occurs in early pregnancy. Cytomegalovirus, the most common congenital infection worldwide, and Toxoplasma gondii, a parasite transmitted through undercooked meat or contact with cat feces, are both recognized causes of congenital disease, though their specific contribution to structural heart defects has been less clearly quantified. This study adds a preconception dimension to that picture, suggesting that the immunological terrain established before pregnancy may matter as much as events during gestation.

The methodological strengths of the study deserve emphasis. With more than 630,000 pregnancies and over 1,300 outcome cases, the analysis had the statistical power to detect associations of modest magnitude that smaller studies would miss. The prospective timing of the exposure assessment is another advantage: infection status and serology were measured at preconception examinations, before any pregnancy outcome was known, which reduces the risk of recall bias and reverse causation that plague studies relying on postnatal reporting. The use of a birth defects registry for outcome ascertainment provides systematic case identification across the province. Sensitivity analyses, in which the researchers re-ran their models under alternative assumptions, produced results consistent with the primary findings, adding confidence that the associations are not artifacts of particular modeling choices.

At the same time, the authors and readers alike must weigh the inherent limits of observational research. An association, however robust, does not prove causation. Seropositivity to cytomegalovirus, rubella, and Toxoplasma gondii reflects past exposure and may correlate with unmeasured characteristics, such as socioeconomic conditions, occupational exposures, dietary patterns, or broader immune profiles, that could themselves influence cardiac development risk. The study was conducted in a single province of China, and seroprevalence of these pathogens varies considerably across regions and income settings, so the absolute risks and even the magnitude of associations may differ elsewhere. The authors also note that the published version was shared early as a citable, peer-reviewed accepted manuscript subject to further editorial refinement, a reminder that details may be updated in the final version of record.

Even with those caveats, the public health implications are considerable. Congenital heart disease imposes a lifelong burden on affected children and families, often requiring surgery, ongoing cardiology care, and in severe cases resulting in early mortality. If preconception infection status genuinely contributes to risk, then the period before pregnancy becomes a critical and currently underused window for intervention. Screening and treating chlamydial infections and candidiasis before conception, counseling women on toxoplasmosis prevention, and ensuring rubella immunity through vaccination well ahead of pregnancy are all established, low-cost measures already embedded in many preconception care frameworks. The findings from Guangdong suggest that such measures may carry benefits beyond the infections themselves, potentially reducing the burden of the most common birth defect. For the millions of couples planning pregnancy each year, the message from this research is that the health of the next generation’s heart may begin taking shape long before the first heartbeat.

Subject of Research: Preconception maternal infection-related exposures and the risk of congenital heart disease in offspring

Article Title: Preconception maternal infection-related exposures and risk of congenital heart disease in offspring: evidence from a large population-based cohort in South China

Article References: Chen, Y., Xu, R., Wei, H., Gu, Q., Liu, Y., Zhu, J., Yang, L., Zhang, Y., & Tan, G. (2026). Preconception maternal infection-related exposures and risk of congenital heart disease in offspring: evidence from a large population-based cohort in South China. BMC Public Health. https://doi.org/10.1186/s12889-026-29782-z

Image Credits: AI Generated

DOI: 10.1186/s12889-026-29782-z

Keywords: congenital heart disease, preconception health, Chlamydia trachomatis, cytomegalovirus, rubella, Toxoplasma gondii, candidiasis, IgG seropositivity, population-based cohort, birth defects registry, maternal infection, Guangdong China