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A 15-year study of nearly 60,000 births shows that congenital syphilis and other STIs continue to endanger babies, as healthcare barriers in remote Australia undermine otherwise effective screening programs.

Study: The association between sexually transmitted infections and pregnancy outcomes in the Northern Territory, Australia: a population-based cohort study. Image credit: Saiful52/Shutterstock.com

Sexually transmitted infections (STIs) are highly prevalent in women of reproductive age. Though often asymptomatic, they can cause severe pregnancy complications. A recent paper in The Lancet examined birth outcomes from a population-based cohort in the Northern Territory, Australia, to assess the relative risk for pregnancy complications with STIs.

Introduction

According to the World Health Organization, there were 374 million new STI cases in 2020, among people between 15 and 49 years, caused by just four notifiable conditions: chlamydia, gonorrhea, trichomoniasis, and syphilis. Most cases are under 35 years of age.

STI rates are increasing in Australia, but most go undiagnosed and untreated. For instance, two out of three chlamydial infections in Australians aged 15-29 years are missed, making it difficult to prevent and control the spread of such infections. The Northern Territory is a particular challenge since the average STI notification rates are much higher than the national average, as much as ten times higher in the case of gonorrhea, and fourfold with chlamydia.

Multiple factors contribute to this situation. The territory is geographically remote, culturally disparate, and has poor healthcare facilities. For instance, only three public hospitals and one private hospital serve an area of 1.4 million square km.

While these high numbers do reflect active surveillance and screening rates, they also suggest poor disease control, especially affecting Aboriginal and Torres Strait Islander peoples, who make up a third of the people living here. These people groups have up to fivefold the rates of syphilis and gonorrhea that non-indigenous people do. The most isolated parts of the Northern Territory have endemic trichomoniasis, which is notifiable only in this part of Australia.

Prior research indicates that STIs during pregnancy reduce the odds of favorable outcomes. Putative or established mechanisms include ascending infection or inflammatory cytokine production, causing decidual inflammation, leading in some cases to premature rupture of the fetal membranes or cervical ripening and dilation. Both mechanisms may trigger preterm birth.

The worst impact is from syphilis, since the Treponema pallidum pathogen crosses the placenta to infect the fetus from 9-10 weeks onwards. It causes large-scale inflammation and injures the placental vasculature. The outcomes include placental insufficiency, poor fetal growth, and stillbirth.

The adverse effects of STIs on pregnancy are largely preventable by timely screening, diagnosis, and antibiotic treatment. Most prior studies have been small or based on detecting a single STI. Indigenous populations have been largely excluded from such studies. The current study examined associations between multiple STIs and poor pregnancy outcomes in a sample with a high percentage of indigenous people and with a substantial STI prevalence.

About the study

The cohort included 59,465 singleton pregnancies, which were stratified by the presence of any of these four notifiable STIs. A type of statistical analysis called Poisson regression was performed to assess robust associations between these diseases and adverse pregnancy outcomes in this cohort. The outcomes of interest were pre-labor rupture of membranes, preterm birth, small-for-gestational age, and stillbirth.

Study findings

Alcohol and smoking were rare in this cohort, with over a third being Aboriginal or Torres Strait Islanders. Trichomonas infection affected 4%, followed by chlamydia (2.6%) and gonorrhea (1.4%), but only 0.2% had syphilis. Of the babies born to this cohort, 51 and 23 had congenital chlamydia and congenital syphilis, respectively, less than 0.1% each. While this reflects generally effective screening, the study emphasized that the 23 cases of congenital syphilis signal ongoing gaps in follow-up and access to care. Congenital gonorrhea rates were low (<20 cases) and were not analyzed in detail.

The study found that the most severe outcomes were linked to congenital syphilis, not maternal infection alone. Congenital syphilis more than tripled the risk of preterm birth (RR 3.34) and doubled the risk of being born small for gestational age (SGA) (RR 2.22). Maternal STIs such as chlamydia, gonorrhea, and trichomoniasis were primarily associated with a higher risk of SGA (RRs 1.86, 1.76, and 1.10, respectively). Among these, gonorrhea was the only maternal infection associated with stillbirth (RR 1.97), and trichomoniasis carried a modestly increased risk of preterm birth (RR 1.23), with SGA remaining the most consistent adverse outcome across all pathogens.

There was no evidence that any maternal STI was linked to premature rupture of membranes or spontaneous preterm birth specifically. The combination of gonorrhea and trichomoniasis during pregnancy nearly doubles the risk for SGA (RR 1.81), but no multiplicative effects were seen for other co-infections.

The researchers found that congenital syphilis was the most severe STI in terms of adverse birth outcomes. While antenatal screening programs in the Northern Territory appear effective overall, especially for syphilis prevention, gaps remain due to logistical, geographical, and cultural barriers, which are likely to explain why 23 congenital syphilis cases still occurred.

The continuing high rate of adverse outcomes in pregnancies complicated by STIs indicates that implementation challenges, rather than screening protocol design alone, are the primary obstacles. The findings corroborate the high risks associated with untreated maternal syphilis reported in prior meta-analyses, but not urban studies. This disparity emphasizes the logistical challenges unique to this setting.

Conclusions

“These findings underscore the importance of addressing barriers to STI screening and treatment prior to and during pregnancy.”

Congenital syphilis continues to cause a significant burden of pregnancy complications, underlining the need for preventive and control measures against this infection. This need is particularly important in regions where the STI burden is high.

The study highlights the need for timely and repeated screening beyond the first trimester, culturally safe care, strengthened follow-up, and improved healthcare infrastructure to reduce these risks, rather than relying solely on behavioral strategies such as abstinence or monogamy counseling, which were not recommended by this study.

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Study sample

A total of 5,709 patients with MDD were assessed; 74.5% were in MDD-ANH and 25.5% were in the Other-MDD cohort (met criteria for MDD but not prominent anhedonia). Patient demographics and baseline characteristics during the 12-month baseline period are displayed in Table 1 for each of the two cohorts. The mean (SD) age in years was greater in the MDD-ANH (41.0, [SD = 15.8]) than the Other-MDD (37.8, [15.0], p < 0.001). A greater percentage of MDD-ANH patients had used Medicare (9.0% for MDD-ANH to 5.5% for Other-MDD, p < 0.001) or Medicaid (7.4% for MDD-ANH vs. 5.7% for Other-MDD, p = 0.033) for their most recent health care encounter prior to index. MDD-ANH patients tended to have more non-psychiatric baseline comorbidities compared to Other-MDD at any point prior to baseline. Mean (SD) of Charlson Comorbidity Index scores were greater among the MDD-ANH patients (0.6 [1.3]) compared to Other-MDD patients (0.5 [1.1], p = 0.020). There were no statistically significant differences in baseline psychiatric comorbidities between the MDD-ANH and Other-MDD groups, though the proportion of patients with ADHD was slightly lower in MDD-ANH (9.7%) compared to Other-MDD (11.3%).

The mean PHQ-9 score at the index date was higher among patients with MDD-ANH (18.2, SD = 4.2) compared to patients with Other-MDD (13.5, SD = 2.9) (Table 1). In addition, the last PHQ-9 score during follow-up was higher among patients with MDD-ANH (9.4, SD = 6.6) compared to patients with Other-MDD (8.1, SD = 5.8) (Table 1).

Analysis of antidepressant treatment patterns is presented in Table 2. In both cohorts, more than 80% of patients were treated with antidepressants and individual psychotherapy during follow-up. In the multivariable analyses, patients with MDD-ANH were more likely to have switched antidepressants (adjusted odds ratio [aOR] = 1.24, 95% CI: 1.07, 1.44, p = 0.004) and were more likely to have augmented antidepressant therapy (aOR = 1.16, 95% CI: 1.02, 1.31, p = 0.021) compared to the Other-MDD group.

The percentage of patients using different pharmacologic therapies at follow-up is presented in Table 2. After adjustment for baseline characteristics, patients with MDD-ANH were more likely to have been treated with SNRIs (aOR = 1.29, 95% CI: 1.13, 1.47, p < 0.001), tricyclic antidepressants (aOR = 1.31, 95% CI: 1.10, 1.56, p = 0.003), mood stabilizers (aOR = 1.32, 95% CI: 1.15, 1.51, p < 0.001), atypical antidepressants (aOR = 1.24, 95% CI: 1.09, 1.40, p < 0.001), and atypical antipsychotics (aOR = 1.51, 95% CI: 1.31, 1.74, p < 0.001) during the follow-up time period.

The percentages of patients in remission (PHQ-9 score < 5), with mild depression (PHQ-9 score 5–9), and patients with persistent depression (PHQ-9 score ≥ 10) by cohort is displayed in Fig. 1. By the end of the 12-month follow-up period, 28.7% of patients in the MDD-ANH achieved remission compared with 32.5% of MDD-Other patients. Persistent moderate to severe depression was present among 44.6% of MDD-ANH patients by end of follow-up compared to 35.1% of MDD-Other patients. After adjustment for baseline characteristics, when compared to the Other-MDD group, patients in the MDD-ANH cohort were significantly more likely to have persistent depression (aOR = 1.50, 95% CI; 1.32, 1.70, p < 0.001) and were significantly less likely to be in remission by the final PHQ-9 assessment (aOR = 0.82, 95% CI: 0.72, 0.94, p = 0.003) (Table 2).

Scientists are one step closer to an anti-aging breakthrough as a ground-breaking drug is being tested and if it is successful, it would become the first-ever approved treatment to slow or even stop the aging process.

The drug, which is known as an anti-necrotic, has undergone the testing as a way to stop necrosis or premature death of cells and living tissues.

According to the Cleveland Clinic, “When the cells in your tissues die, it can affect many different areas of your body, including your bones, skin and other organs. While dead body tissues can be removed, they can’t be brought back to good health.”

However, the first-of-its-kind drug on trial can offer promising hope for longevity.

Even the recent research published in the journal Oncogene has endorsed necrosis as a “pivotal mechanism” in various health problems such as cancer, kidney disease, cardiovascular, and neurodegeneration.

The researchers stated that this new drug “may also hold the key to preserving astronaut resilience and health on long-duration space missions, offering the insights that could reshape human longevity both on and off planet.”

Genesis of the unprecedented drug

The idea of the under-trial anti-necrotic drug stemmed from the study’s lead author Carina Kern, the CEO of the biotech company LinkGevity. Kern says since her childhood, she was inspired to find a way to treat or reverse necrosis when she witnessed the death of her grandmother from an age-related disease.

Prior to Kern’s ground-breaking research, scientists were clueless about the ways to intervene in the natural process of necrosis.

According to her findings, “The crux of necrosis is loss of calcium-ion gradients. Levels of calcium inside the cell are typically 10,000 to 100,000 times lower than outside. Calcium is a key signalling molecule, meaning it controls lots of different processes within your cell. So upon stress, you lose this regulation and initiate multiple pathways in a really destructive manner within the cell.”

Kern’s team has managed to identify for the first that it is possible to block necrosis, but you have to block more than one molecular target. Eventually, through this method the team has successfully suppressed 90 percent of necrosis.

Clinical trials of this anti-necrotic drug will begin later this year and will last for two to three years. The success of this drug will astonishingly open new avenues of anti-aging process.