Stress of Prematurity in the Experience of the COVID-19 Pandemic—Current State of Knowledge

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TL;DR

This narrative review summarizes how the COVID-19 pandemic exacerbated stress in pregnant women and mothers of preterm infants, increasing the risk of preterm birth through mechanisms involving HPA axis activation, inflammation, and vitamin D deficiency. The pandemic heightened maternal anxiety, depression, and social isolation, while also limiting access to care and kangaroo mother care, worsening outcomes for preterm infants and their families. The findings underscore the need for routine mental health screening and non-pharmacological stress-reduction interventions during prenatal care, especially in public health crises.

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**Background:** Preterm birth (before 37 weeks of gestation) accounts for over 50% of long-term morbidity and about 75% of perinatal mortality worldwide. The COVID-19 pandemic introduced widespread social changes—lockdowns, reduced healthcare access, increased stress—that may have exacerbated preterm birth rates. This narrative review aims to assess the impact of pandemic-related stress on pregnant women, mothers of preterm infants, and obstetric complications, particularly preterm birth. The review also explores the role of vitamin D deficiency and the physiological mechanisms linking stress to prematurity.

**Methods:** A comprehensive literature review was conducted using PubMed, Science Direct, and Google Scholar. Keywords included “prematurity,” “pregnancy,” “stress,” “COVID-19,” and their combinations. The search was limited to publications from 2019 onward for COVID-19 and from 2010 onward for other keywords. The review synthesizes findings from multiple studies, including observational studies, case-control studies, and cohort studies, to provide a narrative overview of the current state of knowledge.

**Key Results:** The review reports that maternal stress and anxiety increase placental corticotropin-releasing hormone (CRH) levels, which are associated with preterm birth. SARS-CoV-2 infection itself increases the risk of preterm birth by 60% according to a large U.S. study. Inflammatory cytokines (IL-1β, IL-6, TNF-α) and matrix metalloproteinases (MMP-9) are elevated in stressed pregnancies and COVID-19, promoting cervical ripening and preterm labor. A case-control study by Duran-Chávez et al. (129 preterm cases) found elevated MMP-9 and decreased MMP-2 positively associated with preterm birth. Another case-control study by Lilliecreutz et al. reported that 54% of stressed pregnant women delivered preterm. Freedman et al. showed that exposure to a major stressor (JFK assassination) in the first trimester was associated with preterm delivery (HR 1.17; 95% CI 1.05–1.31). During the pandemic, maternal depression rates nearly doubled compared to pre-pandemic levels (King et al.). Breastfeeding rates among mothers of preterm infants dropped from 86.1% pre-pandemic to 44.8% during the pandemic (Italian study). Kangaroo mother care reduced stress scores on the PSS:NICU and STAI E/R scales, though differences were not statistically significant (p > 0.05). Vitamin D deficiency, exacerbated by reduced sunlight exposure during lockdowns, was linked to increased preterm birth risk through immune dysregulation, hormonal disruption, inflammation, and vascular dysfunction. A Turkish study (2021) found a significant association between low vitamin D levels and COVID-19 severity in pregnant women. A Spanish study (2020) suggested higher vitamin D concentrations may decrease preterm birth and preeclampsia risk.

**Clinical Implications:** The review highlights that pandemic-related stress significantly worsens maternal mental health and preterm birth rates. Routine prenatal care should include screening for behavioral health problems and stress. Non-pharmacological interventions such as yoga, meditation, biofeedback, and expressive writing are affordable, widely available, and effective in reducing stress. Kangaroo mother care should be promoted even during pandemics, as it reduces neonatal mortality by 40%, hypothermia by >70%, and severe infections by 65% (WHO). Vitamin D supplementation may lower endogenous cortisol levels and should be considered in pregnant women, especially during periods of limited sun exposure. The long-term consequences of pandemic stress on preterm infants and their families remain unknown, necessitating further research.