Editor's Note: Commentary based on Louis JM, Mogos MF, Salemi JL, Redline S, Salihu HM. Obstructive sleep apnea and severe maternal-infant morbidity/mortality in the United States, 1998-2009. Sleep 2014;37:843-849.

Background

The risk of obstructive sleep apnea (OSA) increases with pregnancy. This is a clearly established medical fact, yet the impact of OSA on pregnancy remains understudied. Various publications have reported conflicting results on the consequences of OSA in pregnancy outcomes. The heterogeneity of these results is primarily due to the widely different outcome measures used and cohort sizes enrolled. There are, however, a few unequivocal findings that repeat themselves throughout most of the trials. Risk of gestational diabetes and pregnancy-induced hypertension as well as that of thromboembolic events is clearly elevated while the risk of infant morbidity and mortality, such as intrauterine growth retardation (IUGR) or preterm birth, remains controversial.

Methods

The aims of the study were: 1) Estimate the prevalence of OSA in pregnancy by utilizing a large and nationally representative database over a period of 11 years, 2) Assess correlations between OSA among pregnant women and the occurrence of pregnancy-related morbidity and mortality, and 3) Evaluate the impact of obesity on gestational OSA-related morbidity. The authors analyzed data obtained from the largest comprehensive, publicly available U.S. inpatient database, the Nationwide Inpatient Sample (NIS). The NIS was mined for ICD-9 codes for OSA, gestational diabetes, cardiomyopathy, gestational hypertension, preeclampsia and eclampsia, IUGR, preterm delivery, cesarean sections and stillbirth. They also stratified the subjects based on the following demographical data: age group, ethnicity, race, socioeconomic status, type of insurance (government, HMO, PPO), type of hospital where they received care, and whether they lived in urban or rural areas. They also considered covariates of substance use, obesity, and other chronic illnesses. Using logistic regression and the Monte Carlo algorhythm, the authors calculated the odds ratios (OR) for the association of OSA with each outcome. They also did four multivariate models, the first of which was to assess the impact of demographic and behavioral variables in the OSA population, the second of which was for other comorbidites, the third of which was for the role of obesity, and the last of which was for the additive impact of OSA and obesity.

Results

Out of a total of 55 million pregnancy-related hospital discharges from 1998-2009, 3/10,000 were diagnosed with OSA. The prevalence, however, dramatically rose by a factor of 24.4% per year. In 1998 the estimate was 0.7/10,000 and in 2009 7.3/10,000. Women with OSA were more likely to be of low SES, non-hispanic black, older, have used tobacco, alcohol or recreational drugs during pregnancy, had a history of prior C section, and on government insurance. After controlling for all confounding variables the OR of cardiomyopathy was in women with OSA was 9.0 (CI 95% 7.5-10.9), that of CHF 8.9 (CI 95% 7.5-10.7), that of pulmonary edema 7 (CI 95% 4.6-12.2). OSA was also associated with 5.4-fold increase in risk of eclampsia (CI 95% 3.3-8.9), and 2.5-fold increase in preeclampsia (CI 95% 2.2-2.9). The OR for gestational diabetes was 1.9 (CI 95% 1-7-2.1) and that for gestational hypertension was 1.3 (CI 95% 1.1–1.5). Although the risk of premature delivery was modestly increased in women with OSA (OR of 1.2; 95% CI, 1.1–1.4), there was no significant increase in stillbirths or IUGR with OSA. Women with OSA had a five-fold increase in the risk of in-hospital mortality compared to those without OSA, even after adjusting for preexisting chronic morbidities. The annual increase in the prevalence of OSA was commensurate with the annual increase of clinical obesity in the study population. The joint diagnosis of obesity only increased the risk of gestational hypertension, preeclampsia and severe cardiovascular morbidities compared to those with OSA without obesity. All other associations were not influenced by the presence of obesity among women with OSA.

Conclusion

OSA is becoming more prevalent in pregnancy as the pregnant population grows older and more obese. OSA is associated with number of severe, particularly cardiovascular, morbidities and with in-hospital mortality. Treating both OSA and obesity is essential for healthy pregnancies.

Commentary/Perspective

OSA in pregnancy is definitely a risk factor for serious cardiovascular and gestational morbidity and maternal mortality. The prevalence of OSA is dramatically increasing among pregnant women in great part due to increased prevalence of obesity and mean age of pregnant women. Although the risk of stillbirths and IUGR is not associated with OSA, premature birth and maternal morbidities may otherwise impact infant health shortly after birth. In addition, specific demographic groups appear to be more vulnerable to gestational OSA, therefore constituting a focused targets for early detection, education, and both prevention and therapy.

Prior to this large cohort study, the literature was filled with conflicting results, although the majority of papers suggested a strong association between OSA and gestational hypertensive illnesses and diabetes. This study clearly solidifies the risk OSA poses for morbidity and mortality in this sorely understudied population. The diagnosis of OSA is easy and, with the advent of home sleep testing, relatively inexpensive. Its treatment with an auto-titrating continuous positive airway pressure (auto CPAP) is also uncomplicated, safe and effective. There are also pregnancy-specific screening tools for the detection of OSA risk that can be easily implemented and have a high yield. In view of these findings, it is essential that pregnant women, especially those in vulnerable groups such as low SES, gravid obesity, and African Americans, be screened routinely for OSA so that the proper diagnostic and therapeutic interventions can be instituted immediately preventing maternal morbidity, mortality, and potentially also infant morbidity. In order to achieve this, there needs to be educational campaigns targeting both obstetricians and related health care providers (midwives, family medicine physicians, etc.) and the general public.

The question that remains is whether OSA treatment will reverse the risk of these serious cardiovascular illnesses in pregnant women. Large prospective trials are needed to answer that question.

Regardless, this is a sorely under-recognized and serious health issue that can be screened for and treated with relative ease and at only a moderate cost. Early intervention may lead to significant improvement in the wellbeing of both the mother and the infant and prevention of serious chronic diseases quite cost-effective in of itself.

Keywords: African Americans, Alcohols, Cardiomyopathies, Cesarean Section, Chronic Disease, Confounding Factors, Epidemiologic, Continuous Positive Airway Pressure, Diabetes Mellitus, Diabetes, Gestational, Early Intervention, Educational, Eclampsia, Fetal Growth Retardation, Health Maintenance Organizations, Health Personnel, Hispanic Americans, Hospital Mortality, Hypertension, Pregnancy-Induced, Infant, Infant Welfare, Infant, Newborn, Inpatients, International Classification of Diseases, Logistic Models, Maternal Mortality, Midwifery, Mothers, Obesity, Outcome Assessment, Health Care, Pre-Eclampsia, Pregnancy, Pregnancy Outcome, Premature Birth, Prevalence, Prospective Studies, Pulmonary Edema, Risk Factors, Rosa, Sleep Apnea, Obstructive, Social Class, Stillbirth, Illicit Drugs

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