Abstract
Hypertension and depression are common conditions impacting the health of millions of people globally. The prevalence of hypertension in nonpregnant reproductive-aged women in the United States was reported as being 16.5% based on the 2017 American College of Cardiology–American Heart Association guidelines. 1 A recent study analyzing data from the National Health and Nutrition Examination Surveys found that the prevalence of major depression in nonpregnant women aged 20–44 years was 4.8% and minor depression was 4.3%. 2
These conditions are also common in pregnancy. Hypertension in pregnant women can present in several ways: as chronic hypertension, gestational hypertension, or as part of the preeclampsia–eclampsia syndrome. Collectively, these conditions are commonly termed “hypertensive disorders in pregnancy” (HDP). Recent global estimates suggest up to 8% of pregnant women develop preeclampsia. 3 In the United States up to 1.5% of pregnant women are diagnosed as having chronic hypertension at the time of delivery-related hospitalization. 4 Common risk factors for HDP include nulliparity, older maternal age, multiple gestations, preexisting hypertension, obesity, and prior history of preeclampsia. 3,4 The diagnosis of preeclampsia with severe features or eclampsia, especially if preterm, has the greatest adverse impact on maternal, fetal, and neonatal health. 3,5 Complications arising from preeclampsia–eclampsia such as intracerebral hemorrhage or end organ failure make it one of the leading causes maternal mortality worldwide. 5,6 These disorders can also lead to fetal or intrauterine growth restriction (IUGR) from compromised uteroplacental blood flow and preterm birth. 3,4 In the setting of HDP, preterm birth is not always caused by preterm labor but instead is often due to iatrogenic interventions (induction of labor or prelabor cesarean section) that are indicated based on deteriorating maternal or fetal status. 3 –5
It is estimated that 9% of pregnancies are complicated by a diagnosis of major maternal depression with even higher rates noted in the postpartum period. 7 A multivariate analysis of risk factors for depression in pregnant women highlighted the importance of “life stress, lack of social support, and domestic violence.” 8 The impact of a diagnosis of maternal depression on pregnancy complications and birth outcomes has been studied by many investigators. 9 Although the impact does not appear to be as great as for HDP, maternal depression is associated with a small but significant increase in preterm birth 10 but no consistent increase in fetal growth restriction. 11 A large population-based study in Finland demonstrated an association between maternal depression and fetal demise that remained even after controlling for factors such as smoking. 12 Whether pharmacotherapy for depression moderates the effects on birthweight is uncertain. 11 Of great concern is the long-term impact of maternal depression on infant and later childhood health. 13
There is evidence that many pregnancies are complicated by multiple adverse health conditions (comorbidities), which impact pregnancy outcomes. Comorbidities include those in the Elixhauser comorbidity index such as cardiovascular disease, diabetes, and obesity, 14 as well as diagnoses unique to pregnancy such as placental abnormalities, multiple gestation, and previous cesarean section. 15 The maternal morbidity index, which was specifically developed for use in studies addressing severe maternal morbidity and mortality, does not include depression. 15 Given that HDP and depression are relatively common in pregnant women, it is important to know how frequently they occur together as comorbidities and the consequences for maternal, fetal, and neonatal health if a pregnant woman is diagnosed with both conditions.
The study by Mogos et al. (Prevalence, correlates, and outcomes of co-occurring depression and hypertensive disorders of pregnancy) 16 is important because it focuses on HDP and depression in pregnancy as individual and co-occurring morbidities, providing us with nationally relevant prevalence rates and associations with selected outcomes. The outcomes addressed are IUGR, stillbirth, preterm labor, and pregnancy-related hospitalization costs. Using the Nationwide Inpatient Sample (NIS) database from 2002 to 2014 and analyzing ICD-9 codes for >58 million pregnant women at the time of pregnancy-related hospitalization, the authors were able to determine national prevalence rates of HDP (3.99%), depression (1.9%), and HDP plus depression (0.11%) in pregnancy during this 13-year interval. These percentages are probably lower than the true prevalence rates. As the authors note, the study was done using ICD 9 codes and only addressed diagnoses identified and coded for during hospitalization. Pregnant women with a past history of depression or women who developed depression postpartum may not have been accounted for.
The prevalence rates of depression in pregnancy in the absence of HDP increased by 23% during the first 2 years of the study and then by 6.5% annually, whereas rates of depression in pregnancy in women with HDP increased by 8.8% annually. The annual rate increase of HDP in pregnancy without depression was 2.3%. 16 Whether these increases were due to increased awareness and enhanced screening or represent true increases in the development of these conditions in pregnancy cannot be determined from this study. Screening for depression in adults was initially advised by the U.S. Preventative Services Task Force in 200217 and has been progressively incorporated into obstetrical practice since then with regularly updated guidelines. 7 Although the rise in depression diagnoses could be due to changes in screening practices, this is not likely to be the case for HDP. Screening for HDP has been the basis for much of what has historically been done during a prenatal visit (measuring blood pressure and checking for proteinuria), and changes in screening methods are unlikely to have resulted in an increase in HDP-related diagnoses during the study's time period. The increases are more likely due to behavioral, environmental, and biological factors such as the rise in preexisting chronic hypertension, obesity and metabolic syndrome, advancing maternal age, and the increased frequency of multiple gestations.
HDP and depression in pregnancy were found to be independently and jointly associated with increased rates of IUGR, stillbirth, preterm labor, and pregnancy-related hospitalization costs. 16 A strength of this study is that these associations were present after controlling for multiple confounding variables, including those in the Elixhauser comorbidity index, maternal behavioral variables, and pregnancy-specific complications such as gestational diabetes and placental abnormalities. Even more significantly the study addressed the joint associations and relative increased risk due to interaction (RERI) of co-occurring HDP and depression on these outcomes. The authors found that, “Compared to pregnant women without depression and HDP, women with depression and HDP were 3.41 times (AOR = 3.41, 95% CI: 3.15–3.68), 1.94 times (AOR = 1.94, 95% CI: 1.65–2.27), and 4.10 times (AOR = 4.10, 95% CI: 3.89–4.32) more likely to experience IUGR, stillbirth, and preterm labor respectively, even after adjusting for potential demographic and clinical confounders. However, RERI did not show the association to be additive.” In their conclusion the authors write as follows: “Overall, our study indicates that HDP is driving the magnitude of joint association of HDP and depression with adverse neonatal outcomes. The presence of depression with HDP has very minimal effect in increasing the risk of adverse neonatal outcomes including preterm labor, stillbirth, and IUGR.” 16
Although the authors state these are “neonatal outcomes,” apart from stillbirth, this is not the case. These outcomes are more appropriately referred to as pregnancy complications (in the case of preterm labor) or fetal outcomes (in the case of IUGR). Neonatal outcomes refer to outcomes that occur during the neonatal period (from birth to 30 days postbirth). The authors analyzed maternal records, not neonatal records, and provide no information on gestational age at delivery or birthweight. Without this information they cannot conclude that preterm birth (birth before 37 weeks of gestation) was increased. Preterm labor could be considered a proxy for preterm birth, but many cases of preterm labor do not result in preterm delivery 18 and, as noted earlier, preterm births in the setting of HDP are often due to indicated preterm delivery without preterm labor. Similarly, the diagnosis of IUGR or fetal growth restriction during pregnancy relies on estimated gestational age and estimates of fetal size based on ultrasound biometry. Without neonatal birthweight and estimated gestational age at the time of delivery it is difficult to assess the accuracy of the antenatal diagnosis as the neonatal definition of this outcome is a birthweight less than the 10th percentile for gestational age at the time of delivery. 19
Thus, the study by Mogos et al. 16 gives nationally relevant information on the prevalence of HDP, depression, and co-occurring HDP and depression in pregnancy. It provides evidence that these already common conditions are increasing on a yearly basis with accompanying increases in pregnancy-related hospitalization costs. Although HDP and depression were each associated with higher rates of preterm labor, stillbirth, and IUGR, the odds ratios were much higher for HDP. There appeared to be no significant additive effect of depression when both diagnoses were present as comorbidities. However, the individual and joint associations of HDP and depression with the neonatal outcomes of preterm birth and growth restriction at delivery or the outcome of poor infant growth cannot be ascertained from this study.