Introduction
Psoriasis is a severe, non-communicable, and disabling disease that poses a substantial public health concern due to psychological, social, and financial burden. To inform policymakers and healthcare professionals about the impact of this disease on public health, a better understanding of the global burden of psoriasis is required [
1]. Psoriasis is caused by the interaction of several factors, including genetics and environmental factors [
2]. Although succinct studies on the prevalence of psoriasis are published, it is more likely to occur among white populations and people living at higher latitudes. Studies that report information on the incidence of psoriasis are limited. Despite the fact that the pathophysiology of psoriasis is complex and not fully understood [
3], it has been disclosed that type 17 (Th17) helper cells play an important role in pathogenesis and are also associated with adverse pregnancy outcomes [
4].
The reported prevalence of psoriasis is substantially varied in different studies. Earlier estimates of the prevalence of psoriasis in adults range between 0.27% [
5], and 11.4% [
6] with age, sex, geography, ethnicity, genetic, and environmental factors contributing to the variation in the prevalence of the disease [
7,
8]. The incidence rate of psoriasis is the highest among the 15–39 and 50–59 age groups [
9]. Therefore, women of reproductive age may often be at a higher risk of the disease. Treatment of psoriasis is long-lasting and sometimes needs systemic therapies [
10]. In addition, people with psoriasis may have a significantly lower quality of life and greater psychological disorders, including anxiety, sadness, and suicidal ideations [
11]. In addition, psoriasis encompasses a broad clinical range of different skin manifestations, such as fistulations, palmoplantar hyperkeratosis, pustular lesions, plaques, and erythema to-squamous papules. It should be noted that just nearly half of the women with psoriasis have the chance of experiencing clinical remission [
12].
The risk of adverse pregnancy outcomes may increase due to the spread of psoriasis inflammation and psoriasis-related comorbidities such as diabetes, cardiovascular diseases, and depression [
13,
14]. Pregnant women with psoriasis are more likely than healthy pregnant women to experience unfavorable pregnancy outcomes both at the maternal and neonatal levels such as preterm birth, (pre)eclampsia, gestational diabetes, congenital malformations, stillbirth, and low birth weight (LBW) [
15]. Inflammation has been linked to unfavorable pregnancy outcomes, including preterm birth and low birth weight. Elevated levels of proinflammatory cytokines associated with active psoriasis, such as IL-6, C-reactive protein, and tumor necrosis factor-α, have been observed in either the mother's serum or cord blood during pregnancies that lead to preterm birth or small-for-gestational-age neonates [
16,
17]. Furthermore, other inflammatory conditions characterized by similar immune-mediated mechanisms, such as inflammatory bowel disease and rheumatoid arthritis, have also been linked to an increased risk of preterm birth and low birth weight [
18,
19]. Based on the available data, there is conflicting evidence regarding pregnancy outcomes in women with psoriasis [
12]. Some studies have indicated an elevated risk of adverse pregnancy outcomes among women with psoriasis, whereas others have not proved this association [
12,
13]. Consequently, due to the inconsistency of these findings, it remains unclear whether psoriasis has an impact on pregnancy outcomes. In this regard, we conducted a systematic review and meta-analysis of observational studies to shed light on these conflicting results and evaluate the impact of psoriasis on maternal and neonatal outcomes.
Discussion
To obtain a conclusion about the association between maternal psoriasis and the risk of adverse pregnancy as well as neonatal outcomes in pregnant women, we performed a systematic review and meta-analysis by compiling the available evidence. This study showed that psoriasis could increase the risk of some pregnancy-related indicators like gestational diabetes, cesarean delivery, (pre)eclampsia, gestational hypertension, preterm birth, spontaneous abortion, and also some neonatal-related outcomes like Low birth weight, small for gestational age, Apgar score < 7, and stillbirth.
Our findings indicated that psoriasis increased the risk of preterm birth, which was consistent with other studies conducted in the United States (2017), Taiwan (2020), Swedish (2019), and California (2019) [
46‐
49]. However, these results were inconsistent with the study conducted in Denmark (2018) showing no significant relationship between psoriasis and preterm birth [
13]. The diversity between studies could be explained by the different sample sizes. Compared to other studies, the sample size of a study conducted in Denmark included a lower sample size. The identification of increased risk of preterm birth is an important finding, as it plays a key role in neonatal morbidity (congenital malformations, Low birth weight) and mortality [
50,
51]. Preterm birth is complex, and the underlying mechanisms, risk factors, and etiology are not fully understood. Premature birth is associated with increased morbidity and mortality both early and late in life [
48,
52].
Our findings demonstrated that psoriasis increased the risk of cesarean delivery. This finding is consistent with other studies [
9,
13]. However, our result is inconsistent with two studies conducted in Boston, USA (2012) and Taiwan (2011). In the study conducted in Boston, which included a retrospective cohort of 122 mothers with psoriasis, and the study conducted across Taiwan, which included 1,463 mothers with psoriasis, it was shown that there was no association between cesarean delivery and psoriasis [
53,
54]. In the present study and other studies, the risk of cesarean delivery increased in women with psoriasis, which is an expected result because an increased risk of cesarean delivery for chronic inflammatory diseases has been described in the literature [
13,
48,
55,
56].
The results showed that psoriasis increased the risk of gestational diabetes, (pre)eclampsia, gestational hypertension, and spontaneous abortion. These findings are in line with several studies [
13,
47,
57]. Gestational diabetes and gestational hypertension were associated with the development of diabetes and cardiovascular diseases in later stages of life, showing the benefits of preventive measures in this group [
58]. In our study, women with psoriasis had an increased risk of (pre)eclampsia, regardless of severity. Our finding regarding the increased risk of (pre)eclampsia in women with severe psoriasis is consistent with a previous population-based study in Taiwan. This study found a positive association between severe psoriasis and Pre-Eclampsia. However, mild psoriasis was not associated with (pre)eclampsia. Such differences may be explained by the relatively limited number of psoriasis patients in the previous study and the different definitions of psoriasis severity used [
54].
We found that psoriasis had a significant impact on some neonatal outcomes like Low birth weight, small for gestational age, Apgar score < 7, and stillbirth. These findings are consistent with several studies conducted around the world [
13,
49,
54]. A study conducted in Sweden showed that no increased risks were observed for stillbirth and an Apgar score < 7, which is inconsistent with the current study [
48]. Available pieces of evidence suggest that increased immune activity in psoriasis could be related to a higher risk of giving birth to Low-birth -weight infants. In support of this finding, it should be noted that immune disorders, like rheumatoid arthritis and inflammatory bowel disease, are associated with pregnancy complications, including Low birth weight and preterm birth [
54].
An increased risk of adverse pregnancy and neonatal outcomes associated with psoriasis has been cited in many sources [
13,
46,
49,
52]. Quantifying additional risks and associated pathways provides insight into the underlying causes of adverse pregnancy and neonatal outcomes and can shape intervention strategies [
59]. As the disease affects the risk of preterm delivery in affected women, special attention to pregnant women is warranted. Women with psoriasis should be monitored individually during pregnancy, and an intervention aimed at preventing pregnancy complications should be done. Clinically, these interventions can be implemented with counseling and prevention efforts, especially in the case of (pre)eclampsia or high blood pressure for women with psoriasis. Both dermatologists and gynecologists should be familiar with the potential consequences of pregnancy in women with psoriasis and monitor their health during pregnancy as well as their infants. It may be an important goal, but with the emergence of new therapeutic options and the continuous collection of more data for their safety during pregnancy, it has become more realistic and important [
13,
47,
48,
53,
54,
57].
This study has four limitations. First, due to some biases (selection, or information biases) in the observational studies, the interpretation of evidence from observational studies requires caution. Therefore, causal links of risk estimates cannot be determined based on the nature of observational studies. Second, although the quality of included studies was generally high, not all studies were adequately adjusted for all potential confounders. We could not fully control the confounding factors either. This may lead to underestimation or overestimation of the risk estimates for the presence of psoriasis diseases. Third, various sources of heterogeneity existed in the included studies possibly due to the varied study designs, data materials, analytical approaches, periods covered, as well as the quality of the studies. Fourth, we had to omit several studies due to different definitions of psoriasis, or inadequate presented information. It is important to mention that the calculated measures could change if we had included the removed studies.
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