Dose-Response Risk: How Multiple Maternal Chronic Conditions Shape Neonatal Morbidity and Mortality

Dose-Response Risk: How Multiple Maternal Chronic Conditions Shape Neonatal Morbidity and Mortality

The Rising Tide of Maternal Multimorbidity

In the evolving landscape of obstetric and neonatal medicine, the profile of the pregnant patient is undergoing a significant demographic and clinical shift. Advances in medical management and shifts in societal trends have led to an increasing number of individuals entering pregnancy with preexisting chronic health conditions. Recent data suggests that nearly 16% of pregnant individuals now present with multiple chronic conditions (MCC), defined as the presence of two or more chronic illnesses. While the impact of multimorbidity on maternal outcomes—specifically the dose-response relationship between the number of conditions and severe maternal morbidity—is well-documented, the implications for the newborn have remained less clear. A landmark population-based cohort study conducted in Ontario, Canada, now provides critical evidence regarding the association between maternal MCC and severe neonatal morbidity or mortality (SNM-M).

Study Methodology: A Decade of Population-Level Data

To address the knowledge gap surrounding neonatal outcomes, researchers utilized a robust dataset from Ontario, Canada, covering all live births between 2012 and 2021. This population-based cohort study included 1,018,968 newborns. The primary exposure of interest was maternal MCC, measured within the two years preceding conception to ensure that the conditions were truly preexisting rather than pregnancy-induced (such as gestational diabetes or preeclampsia).

The researchers categorized maternal health status into four tiers: zero chronic conditions, one condition, two conditions, and three or more conditions. Furthermore, the study examined specific subsets of MCC, including MCC complexity (defined as three or more conditions across three or more distinct body systems), cardiometabolic MCC (co-occurring conditions such as hypertension and diabetes), and MCC severity (proxied by a prenatal hospitalization for a chronic illness). The primary outcome, SNM-M, was a composite measure including severe neonatal complications or death within the first 28 days of life.

Key Findings: The Escalating Risk Profile

The results of the study demonstrate a clear and significant dose-response relationship. As the number of maternal chronic conditions increased, so did the risk of adverse neonatal outcomes. In the cohort, newborns of mothers with no chronic conditions served as the reference group. After adjusting for variables such as maternal age, parity, immigration status, income quintile, and rurality, the adjusted relative risks (aRRs) for SNM-M were as follows:

– 1 Chronic Condition: aRR 1.26 (95% CI, 1.24-1.28)
– 2 Chronic Conditions: aRR 1.58 (95% CI, 1.54-1.62)
– 3 or More Chronic Conditions: aRR 2.01 (95% CI, 1.94-2.09)

These data points indicate that newborns born to mothers with three or more chronic conditions face double the risk of severe morbidity or mortality compared to those born to mothers with no chronic conditions.

The Impact of Complexity and Cardiometabolic Clusters

Beyond the mere count of conditions, the nature of the multimorbidity played a vital role in neonatal risk. Complexity—defined by multi-system involvement—showed an aRR of 1.97, nearly identical to the risk posed by the count of three conditions. However, the risk was even more pronounced in the presence of cardiometabolic MCC, which yielded an aRR of 2.67 (95% CI, 2.24-3.19). This highlights the particular vulnerability of newborns when maternal health is compromised by the synergistic effects of metabolic and cardiovascular dysfunction, which are known to impair placental development and fetal perfusion.

The Role of Maternal Disease Severity

The most striking risk elevation was observed in cases of severe MCC, where the mother had been hospitalized for a chronic illness prior to delivery. In these instances, the aRR for SNM-M reached 3.11 (95% CI, 2.55-3.79). This suggests that the stability and management of chronic conditions are perhaps as important as the diagnosis itself when assessing neonatal risk.

Mechanistic Insights and Clinical Implications

The biological plausibility of these findings rests on the cumulative physiological stress that multiple chronic conditions place on the maternal-fetal unit. Chronic inflammation, vascular dysfunction, and suboptimal metabolic environments associated with conditions like autoimmune disorders, hypertension, and renal disease can lead to placental insufficiency. This, in turn, increases the likelihood of intrauterine growth restriction, preterm birth, and neonatal metabolic instability.

From a clinical perspective, these findings necessitate a shift in how we approach preconception and prenatal care. The dose-response relationship suggests that there is no ‘safe’ threshold of multimorbidity; rather, risk is a continuum. Clinicians should consider the following strategies:

1. Enhanced Preconception Counseling: For individuals with MCC, the preconception period is a critical window for optimizing disease control and reviewing medications. Reducing the ‘severity’ of a condition before pregnancy may directly translate to improved neonatal outcomes.
2. Multidisciplinary Care Models: Management of MCC requires integration between primary care, maternal-fetal medicine specialists, and relevant subspecialists (e.g., cardiologists, endocrinologists).
3. Increased Neonatal Surveillance: Identifying mothers with MCC—particularly cardiometabolic or complex clusters—allows for better preparation by neonatal intensive care units (NICU) and pediatric teams during the delivery and immediate postpartum period.

Study Limitations and Strengths

A major strength of this study is its massive sample size and the use of a single-payer healthcare system database, which minimizes selection bias and ensures comprehensive follow-up. However, limitations include the potential for unmeasured confounding variables, such as behavioral factors (e.g., diet, exercise) or specific environmental exposures that could not be fully captured in administrative data. Additionally, while the study identifies associations, it cannot definitively prove causality for each individual condition within an MCC cluster.

Conclusion: A Path Toward Better Neonatal Health

The study by Brown et al. serves as a powerful reminder that neonatal health is inextricably linked to maternal systemic health long before the moment of conception. As the prevalence of MCC continues to rise among reproductive-aged populations, health systems must adapt to provide more nuanced, integrated care. By recognizing the escalating risks associated with maternal multimorbidity, clinicians can better identify high-risk pregnancies, optimize maternal health, and ultimately provide the enhanced support necessary to safeguard the lives of the most vulnerable newborns.

References

1. Brown HK, Fung K, Cohen E, et al. Multiple Maternal Chronic Conditions and Risk of Severe Neonatal Morbidity and Mortality. JAMA Netw Open. 2026;9(1):e2555558. doi:10.1001/jamanetworkopen.2025.55558.
2. Admon LK, et al. Trends in Chronic Condition Prevalence Among Deliveries in the United States, 2005-2014. Obstetrics & Gynecology. 2018.
3. Gubhaju L, et al. The impact of maternal multimorbidity on adverse birth outcomes. BMC Pregnancy and Childbirth. 2020.

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