Original ArticleMaternal obstructive sleep apnea and neonatal birth outcomes in a population based sample
Introduction
Obstructive sleep apnea (OSA), a condition on the spectrum of sleep disordered breathing, is characterized by recurrent intermittent hypoxemia, airflow limitation and repetitive arousals from sleep. Dynamic pregnancy physiology predisposes women to the development of OSA. Upper airway narrowing and edema related to decreased oncotic pressure and hormonal influences, reduced functional residual capacity and chest wall compliance, as well as possible weight gain may all predispose pregnant women to the development or worsening of preexisting sleep disordered breathing. Furthermore, OSA is a component of sleep disordered breathing [1]. In addition, nearly half of women of childbearing age are entering pregnancy either overweight or obese in countries like the United States [2], and the prevalence of OSA now exceeds 10% in pre-menopausal women [3]. OSA likely affects a significant proportion of women entering pregnancy, with a higher proportion of women having OSA in late pregnancy [4].
Possibly due to repetitive hypoxemia and sympathetic activation, OSA and sleep disordered breathing have been linked to maternal outcomes such as hypertensive disorders of pregnancy and gestational diabetes [5], [6], [4], [7], as well as neonatal outcomes including prematurity [8] and growth restriction [8], [9], even after adjustment for multiple covariates. In one study, neonates born to mothers with OSA have also been shown to require an intensive care unit admission more often than those born to mothers without OSA [10]. However, there have been no reports to date examining an association of sleep disordered breathing with congenital anomalies.
The etiology of congenital malformations is usually multifactorial and includes an inflammatory or infectious milieu, genetic susceptibility, or environmental and epigenetic changes [11], [12], [13], [14]. Given a link between OSA and inflammation, and epigenetic changes, we hypothesized that exposure to maternal OSA in-utero would be associated with an increased risk of congenital anomalies. The aim of this study was to examine whether infants born to women with OSA are at an increased risk of having congenital anomalies, and to confirm prior reports of a potential risk for preterm birth, growth restriction, and a need for intensive neonatal care. As congenital anomalies are a rare outcome of pregnancy, large datasets are needed to examine such associations. Furthermore, adverse neonatal outcomes and congenital anomalies have devastating effects on life-long health and are associated with high costs to individuals and society. As OSA is easy and safe to treat, identification of an association of OSA with these negative outcomes paves the way for future research; which could examine causality, assessing and optimizing the impact of therapy on these outcomes, and holds the prospect of offering potential preventive strategies to women at risk.
Section snippets
Study population, setting, and study period
The National Perinatal Information Center (NPIC) data is a membership organization consisting of 95 perinatal centers across all geographic census divisions of the U.S. defined by the American Hospital Association [15], that submit clinical and financial information quarterly. Data are validated and compiled into the Perinatal Center Data Base (PCDB), which consists of both maternal and neonatal hospital discharge data, the latter occurring from birth to 28 days after birth. Multiple levels of
Maternal characteristics
From 1,606,190 newborn records, a total of 1,423,099 live newborns were linked to maternal records after excluding duplicates (Fig. 1). Hospitals contributing to the data have been detailed previously [5]. In brief, hospitals in the southern part of the U.S. contributed 43.3% of all patients to the dataset. Hospitals in metropolitan areas and teaching hospitals contributed the highest proportion of records to the dataset (97.2% and 73.6% respectively). Hospitals with more than 5000 deliveries
Discussion
This study is the first to examine and show an association of in-utero exposure to OSA with the presence of congenital anomalies in the offspring. The study also demonstrates a higher risk of admission to the NICU, a higher risk of requiring resuscitation and airway intubation at birth, and for being born preterm. There was no significant association between OSA status and small baby size for gestational age, calculated based on birthweight, sex, and gestational age. After adjusting for
Conclusions
In conclusion, infants born to mothers with OSA are at a higher risk of having congenital anomalies compared to unexposed infants. In addition, OSA diagnosis is associated with an elevated risk of neonatal intensive care admission, higher level of care and preterm birth. Though this study does not establish causation between OSA and congenital anomalies and the occurrence of the latter is related to complex interactions between the genetic, environmental and the biological milieu, the data
Guarantor
Ghada Bourjeily is the guarantor of the paper and takes responsibility for the integrity of the work as a whole, from inception to published article.
Funding
This study was partly supported by department funds from the Women's Medicine Collaborative at The Miriam Hospital. Study funders had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
GB is funded by the National Institutes of Health R01HD078515 and R01HL130702
CRediT authorship contribution statement
Ghada Bourjeily: Conceptualization, Funding acquisition, Investigation, Methodology, Writing - original draft, Writing - review & editing. Valery A. Danilack: Conceptualization, Formal analysis, Data curation, Investigation, Methodology, Writing - original draft, Writing - review & editing. Margaret H. Bublitz: Conceptualization, Investigation, Methodology, Writing - review & editing. Janet Muri: Data curation, Writing - review & editing. Karen Rosene-Montella: Conceptualization, Funding
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