The Impact of Opium Consumption on Inflammatory Factors in Umbilical Cord Blood and Maternal Blood Postpartum: A Potential Contributor to Neonatal Complications

Abstract

Opium addiction during pregnancy can have significant effects on the activity of the immune system as well as on pregnancy outcomes. A study was conducted comparing opium-addicted pregnant women to healthy pregnant women. Blood samples were taken from the maternal vein and umbilical cord immediately after delivery to measure concentrations of inflammatory markers. The results showed that the opium-addicted group had significantly higher levels of IL-6, IL-10, CRP, C3, and C4 in both maternal and cord blood samples compared to the control group. Additionally, adverse pregnancy outcomes such as NICU admissions, neonatal deaths, and low Apgar scores were more prevalent in the opium-addicted group. These findings suggest that opium addiction during pregnancy can lead to postpartum inflammation and negatively impact pregnancy outcomes. It is important to address opium addiction and provide appropriate support and treatment to pregnant women to improve pregnancy outcomes and reduce the risk of complications.

Keywords

opium inflammation pregnancy outcome umbilical cord

Introduction

Opium addiction poses a significant public health challenge, particularly among women in Iran, where it is the most common substance abuse issue (Ghazavi, Mosayebi, et al., 2013; Maghsoudlou et al., 2018; Saleh Gargari et al., 2011; Sharifian et al., 2011; Soltaninejad & Shadnia, 2018; Zarghami, 2015). Traditionally, opium has been used for both recreational and medicinal purposes, including the treatment of diarrhea, insomnia, and pain (Ghazavi, Mosayebi, et al., 2013; Yarahmadzehi et al., 2020; Zarghami, 2015). The implications of opium use during pregnancy are profound, affecting the health and well-being of both the mother and the developing fetus (Maghsoudlou et al., 2017). While opium contains alkaloids like morphine and codeine, known for their potent analgesic effects (Yarahmadzehi et al., 2020), its consumption during pregnancy is linked to a range of adverse outcomes with lasting repercussions (Maghsoudlou et al., 2017). The research presented herein addresses a critical gap in our understanding of the consequences of opium use during pregnancy, particularly its impact on maternal health. Women who consume opium while pregnant are more susceptible to complications such as preterm labor, premature rupture of membranes, preeclampsia, and conditions leading to stillbirth and placental abruption (Fanaei et al., 2020; Lind et al., 2017). These complications not only present immediate risks but also predispose newborns to long-term health issues (Fanaei et al., 2020; Lind et al., 2017; Maghsoudlou et al., 2017). Moreover, the transplacental passage of opium’s alkaloids can adversely affect fetal development, increasing the risk of conditions like intrauterine growth restriction (IUGR), low birth weight, and premature birth (Bornavard & Fanaei, 2020; Fanaei et al., 2020; Liang et al., 2016; Lind et al., 2017; Maghsoudlou et al., 2017). Infants exposed to opium in utero may also suffer from neonatal abstinence syndrome (NAS), which can manifest as irritability, feeding difficulties, respiratory distress, seizures, and developmental delays (Kopcza & Singh, 2016). Despite the known risks, there is limited information on how opium affects the female immune system during pregnancy, with most research focusing on male subjects (Ghazavi, Mosayebi, et al., 2013;Liang et al., 2016). Some of the negative effects of opioids in men have been demonstrated through their interference with the immune system’s activity and elevation of inflammation levels (Ghazavi, Mosayebi, et al., 2013; Liang et al., 2016).

This study seeks to bridge this knowledge gap by investigating the impact of opium use on inflammatory markers in both maternal and fetal contexts. Understanding this relationship is crucial for developing interventions that improve maternal-fetal health and mitigate the long-term effects of opium exposure. This study is guided by the following research questions: First: How does opium addiction during pregnancy affect inflammatory markers in maternal blood? Second: What is the impact of maternal opium addiction on inflammatory markers in umbilical cord blood?

By assessing the influence of opium addiction on inflammatory markers in maternal and umbilical cord blood, this study aims to elucidate the underlying mechanisms that contribute to adverse maternal and fetal outcomes. The findings are expected to inform healthcare practices, influence public health policies, and enhance the well-being of pregnant women and their children.

Materials and Methods

The present study was an analytical cross-sectional study. The study protocol was approved by Faculty of Medical Ethics Committee (ethical code: IR. ZAUMS. REC.1393.7251). Participants were selected using the convenience sampling method for this study. A total of thirty-five pregnant women with opium addiction and thirty-five healthy pregnant women who presented for delivery at maternity hospitals were included in the study. To calculate the sample size, Cohen’s table was used for the two-tailed test, α = 0.05, the test power was 80% and the effect size was 0.7. The sample size was determined to be 35 in each group. In the case group, women consumed over 2 g of crude opium orally daily for a minimum of one year (Fanaei et al., 2020; Ghazavi, Mosayebi, et al., 2013; Ghazavi, Solhi, et al., 2013), while non-addicted women were chosen for the control group.

The inclusion criteria for the study were as follows: individuals between the ages of 18 and 40, with both physical and mental health, not using hormonal medications, anti-inflammatory or antidepressant drugs, consuming at least 2 gr of crude opium orally per day for a minimum of one year, not currently participating in any other studies, and having a gestational age between 38 and 40 weeks. Exclusion criteria were as having any illness, smoking cigarette, and undergoing addiction treatment with medications such as methadone. After obtaining approval from the Ethics Committee, the study proceeded with sample selection. The participants were provided with an explanation of the study’s significance, objectives, potential applications, and the confidentiality of their information. Written informed consent was then obtained from each participant. Demographic data, including age, gestational age, and weight, were collected using a questionnaire that covered demographic characteristics and inclusion/exclusion criteria. Blood samples were collected immediately after delivery from both the maternal vein and umbilical cord. The blood samples were then processed using a centrifuge at 3500 r/min for 10 minutes to separate the serum, which was subsequently stored in a freezer at −70°C until the measurement of inflammatory markers. ELISA kits were used to measure inflammatory markers C3, C4, CRP, IL-6 and IL-10 (all kits were purchased from Zellbio, Germany).

The researcher used a checklist to assess the various outcomes of pregnancy, such as stillbirth, anomalies, hypertension, and the presence of meconium in the amniotic fluid, admission to NICU, respiratory problems, and resuscitation. Additionally, the researcher recorded and measured the 1-min Apgar scores and birth weight. SPSS software version 26 was used to analyze the data. The independent sample t test and mean and standard deviation (SD) were utilized to describe social demographic characteristics. The Shapiro Wilks test was initially conducted to examine the normal distribution of data. The independent sample t test was employed to compare CRP, C3, C4, IL-6, and IL-10 concentrations between the case and control groups. To compare the outcomes of pregnancy,T test, Mann-Whitney test, Chi-square test, and Fisher’s exact test were performed. Pearson’s correlation coefficient, Spearman correlation coefficient and point-biserial correlation coefficient were used to determine the relationship between inflammatory factors and pregnancy outcomes. In all tests, a significance level of less than 0.05 was considered.

Results

Table 1 summarizes the socio-demographic characteristics of the participants. According to an independent sample t test, there was no significant difference in mothers’ age and gestational age between the case and control groups.

Table 1.

Demographic Characteristics of the Participants of the Study.

Variable	Groups		p-value
	Control	Addict
	Mean ± SD	Mean ± SD
Mothers’ age (year)	29.4 ± 6.6	29.7 ± 7.1	0.9085
Gestational age (week)	38.2 ± 0.6	38.7 ± 1.6	0.0810
Mothers’ weight (kg)	61.5 ± 9.7	55.8 ± 8.4	0.0254

Figure 1(a) demonstrates that the mean serum C3 concentration of addicted mothers (2.321 ± 1.226 g/L) was significantly higher compared to the control group (1.685 ± 0.667 g/L) (p = .014). Moreover, in line with the blood samples from the mothers, the mean C3 concentration in umbilical cord blood of newborns from addicted mothers was significantly higher (1.557 ± 1.137 g/L) than that of the control group (1.019 ± 0.314 g/L) (p = .0152) (Figure 1(a)).

The analysis of samples also revealed a significant increase in the mean C4 concentration in cord blood of addicted mothers (0.55 ± 0.7043 g/L) compared to the control group (0.188 ± 0.07 g/L) (p = .007) (Figure 1(b)). Additionally, the addicted mothers showed significantly higher levels of serum CRP (13.69 ± 13.83 mg/L) compared to the control group (7.18 ± 6.82 mg/L) (p = .02) (Figure 1(c)).

Similar to the CRP level in mothers’ blood, the umbilical cord blood of addicted mothers exhibited significantly higher CRP levels (3.324 ± 4.964 mg/L) compared to the control group (1.169 ± 1.016 mg/L) (p = .023) (Figure 1(c)). The opium addicted group had significantly higher levels of IL-6 (p < .0001) and IL-10 (p < .0001) in mothers’ blood compared to the control group (Figure 1(d)–(e)). Similarly, IL-6 (p < .0001) and IL-10 (p < .0001) levels in the umbilical cord of the addicted group were noticeably higher than those in the control group (Figure 1(d)–(e)).

Table 2 presents a comparison of adverse pregnancy outcomes between the case and control groups. The results show that there was a significant difference in NICU admission (p = .04), neonatal death (p = .04), Apgar score (p = .02) and birth weight between the two groups (p = .005).

Table 2.

Comparison of Adverse Pregnancy Outcome Between Case and Control Groups.

Adverse pregnancy outcomes		Groups		p Value
Adverse pregnancy outcomes		Case Frequency (percent) or mean ± SD	Control Frequency (percent) or mean ± SD	p Value
NICU admission	Yes	11 (32)	4 (12)	0.04^‡
NICU admission	No	24 (68)	31 (88)	0.04^‡
Congenital anomalies	Yes	2 (6)	0	0.49^■
Congenital anomalies	No	33 (94)	35 (100)	0.49^■
Neonatal death	Yes	3 (9)	1 (3)	0.04^‡
Neonatal death	No	32 (91)	34 (97)	0.04^‡
Hypertension	Yes	2 (6)	3 (9)	0.64^‡
Hypertension	No	33 (94)	32 (91)	0.64^‡
Meconium contaminated amniotic fluid	Yes	6 (18)	2 (6)	0.13^‡
Meconium contaminated amniotic fluid	No	29 (82)	33 (94)	0.13^‡
Respiratory problems	Yes	5 (15)	2 (6)	0.23^‡
Respiratory problems	No	30 (85)	33 (94)	0.23^‡
Neonatal resuscitation	Yes	5 (15)	2 (6)	0.23^‡
Neonatal resuscitation	No	30 (85)	33 (94)	0.23^‡
Apgar score		8 ± 1	9 ± 1	0.02^*
Birth weight (gr)		2799 ± 347	3105 ± 423	0.005^∏

^‡Chi-square, *T test, ^∏ Mann-Whitney, ■Fisher’s exact test.

The point-biserial correlation coefficients, Spearman correlation coefficient and Pearson coefficients were utilized to determine the connection between inflammatory factors and outcomes. The findings revealed that the C3 level in the mother’s blood is significantly positively related to admission to NICU, neonatal death, meconium, respiratory disorders, resuscitation, and gestational hypertension. Additionally, there is a positive significant association between cord blood C3 level and NICU admission, neonatal death, anomaly, meconium, respiratory disorders, and resuscitation. Moreover, a positive significant association exists between maternal blood C4 level and NICU admission, neonatal death, anomaly, meconium, and gestational hypertension. Furthermore, there is a positive significant association between cord blood C4 level and NICU admission, neonatal death, meconium, respiratory disorders, and resuscitation. The mother’s CRP level demonstrates a positive relationship with NICU admission and meconium. Cord blood CRP is significantly associated with NICU admission, neonatal death, anomaly, meconium, respiratory problems, and resuscitation. Maternal IL-6 has a significant negative relationship with the weight of the neonate. IL-6 of the umbilical cord displays a positive and significant relationship with admission to the NICU and meconium. Mother’s IL-10 has a negative significant relationship with birth weight. IL-10 of the umbilical cord has a positive significant relationship with anomaly but demonstrates a negative significant relationship with Apgar (Table 3).

Table 3.

Correlation of Inflammatory Factors and Neonatal/Pregnancy Complications in Women Addicted to Opium.

Outcome of pregnancyInflammatory factors	NICU admission	Congenital anomalies	Neonatal death	Hypertention	Meconium contaminated amniotic fluid	Respiratory problems	Neonatal resuscitation	Apgar score	Birth weight (gr)
Outcome of pregnancyInflammatory factors	Point-biserial correlation coefficient	Point-biserial correlation coefficient	Point-biserial correlation coefficient	Point-biserial correlation coefficient	Point-biserial correlation coefficient	Point-biserial correlation coefficient	Point-biserial correlation coefficient	Pearson’s correlation coefficient	Spearman correlation coefficient
C3 M	r = 0.52p < .0001	r = 0.22p = .07	r = 0.26p = .03	r = 0.26p = .03	r = 0.43p < .0001	r = 0.31p = .01	r = 0.31p = .01	r = −0.2p = .11	r = −0.09p = .45
C3 U	r = 0.35p = .005	r = 0.31p = .01	r = 0.48p < .0001	r = 0.13p = .3	r = 0.28p = .02	r = 0.31}p = .01	r = 0.31p = .01	r = −0.11p = .37	r = 0.03p = .82
C4 M	r = 0.41p = .001	r = 0.36p = .004	r = 0.27p = .03	r = 0.25p = .04	r = 0.33p = .009	r = 0.18p = .15	r = 0.18p = .15	r = −0.2p = .12	r = - 0.05p = .65
C4 U	r = 0.44p < .0001	r = 0.18p = .15	r = 0.39p = .002	r = 0.06p = .65	r = 0.64p < .0001	r = 0.48p < .0001	r = 0.48p < .0001	r = 0.09p = .48	r = −0.03p = .8
CRP M	r = 0.28p = .02	r = 0.17p = .16	r = 0.07p = .53	r = 0.21p = .08	r = 0.3p = .01	r = 0.23p = .056	r = 0.23p = .056	r = 0.02p = .83	r = −0.18p = .14
CRP U	r = 0.61p < .0001	r = 0.47p < .0001	r = 0.49p < .0001	r = 0.24p = .055	r = 0.44p < .0001	r = 0.48p < .0001	r = 0.48p < .0001	r = −.03p = .77	r = 0.14p = .26
IL6 M	r = 0.11p = .36	r = 0.03p = .76	r = −.0.03p = .75	r = −0.18p = .12	r = 0.06p = .6	r = −0.01p = .89	r = −0.01p = .89	r = −0.16p = .17	r = −0.35p = .002
IL6 U	r = 0.35p = .002	r = 0.18p = .12	r = 0.17p = .14	r = −0.04p = .74	r = 0.29p = .01	r = 0.23p = .055	r = 0.23p = .055	r = - 0.11p = .35	r = −0.23p = .052
IL 10 M	r = 0.16p = .18	r = 0.02p = .87	r = 0.03p = .74	r = −0.1p = .4	r = 0.1p = .39	r = 0.09p = .46	r = 0.09p = .46	r = −0.09p = .46	r = - 0.28p = .01
IL10 U	r = 0.18p = .12	r = 0.25p = .03	r = 0.07p = .51	r = −.02p = .81	r = 0.09p = .45	r = 0.05p = .63	r = 0.05p = .63	r = −0.25p = .03	r = −0.2p = .08

M: Mothers’ blood, U: Umbilical cord blood.

Discussion

The findings of this study demonstrate that opium consumption during pregnancy leads to increased levels of inflammatory factors in both maternal blood and umbilical cord blood. Specifically, the levels of IL-6 and IL-10, as well as CRP, C4, and C3, were significantly higher in mothers who were addicted to opium compared to the control group.

IL-6 and IL-10 are known to be pro-inflammatory cytokines that play crucial roles in the immune response. Elevated levels of IL-6 and IL-10 in maternal blood indicate an increased immune response and inflammation. To maintain and continue normal pregnancy, accurate balance between secretion of pro-inflammatory and anti-inflammatory cytokines is needed to support growth of the embryo and placenta (Mardini et al., 2016; Thaxton & Sharma, 2010). The results of this study suggest that opium consumption during pregnancy can trigger an exaggerated immune response, leading to higher levels of IL-6 and IL-10 in the maternal bloodstream.

IL-6 plays a crucial role in the reproductive system and the development of embryos during pregnancy (Mardini et al., 2016; Thaxton & Sharma, 2010). It has various functions, such as regulating embryo implantation, ensuring proper growth of the placenta and fetus, and aiding in the adaptation of the immune system to tolerate pregnancy (Prins et al., 2012). As a pro-inflammatory cytokine, IL-6 works through multiple mechanisms (Gabay, 2006). It stimulates T- and B-cells, promotes the production of other pro-inflammatory cytokines like INF-y, and is involved in the production of CRP (Gabay, 2006). Additionally, IL-6 is associated with chronic inflammatory responses (Gabay, 2006).

Numerous studies have demonstrated that IL-6 levels increase in certain disorders related to pregnancy, including infertility, recurrent abortion, preeclampsia, and preterm delivery (Graham et al., 2018; Prins et al., 2012; Rudolph et al., 2018). Furthermore, higher levels of IL-6 during pregnancy in mothers have been linked to an increased risk of neurological and psychiatric disorders in their children (Graham et al., 2018; Prins et al., 2012). Rudolph et al. (2018) found that maternal inflammation during pregnancy can impact the development of the child’s brain (Rudolph et al., 2018). They revealed that elevated IL-6 levels in mothers during pregnancy are associated with impaired formation of neonatal neural circuits and reduced working memory at the age of two (Rudolph et al., 2018).

Graham et al. (2018) demonstrated that increased IL-6 levels in mothers’ blood during pregnancy can affect fetal brain development, particularly the structure of the amygdala, and contribute to behavioral phenotypes associated with psychiatric disorders ( Graham et al., 2018). Similarly, Rasmussen et al. (2019) indicated that elevated IL-6 levels and systemic inflammation in pregnant mothers can lead to changes in the frontolimbic white matter of the brain and cognitive impairment in early life (Rasmussen et al., 2019).

The findings of our study indicated an increase in IL-10 levels in both the mothers’ blood and the umbilical cord blood of individuals addicted to opium. In non-pregnant women, IL-10 serves as an agent that suppresses immune responses when faced with inflammatory events (Thaxton & Sharma, 2010). During pregnancy, IL-10 is secreted by various cells in the mother and the fetus (Thaxton & Sharma, 2010). It is worth noting that the concentration of IL-10 rises throughout a normal pregnancy, reaching its peak in the third trimester (Thaxton & Sharma, 2010). The presence of IL-10 during pregnancy plays a role in suppressing the maternal immune system, thereby facilitating the acceptance of the embryo tissue and supporting the normal processes of pregnancy (Thaxton & Sharma, 2010).

IL-10 exerts its anti-inflammatory effects by reducing the secretion of other inflammatory cytokines, such as IL-6, IL-1, IL-12, and TNF-α (Cheng & Sharma, 2015). In the context of this particular study, it is possible that IL-10 levels were increased even further in response to the heightened levels of inflammation observed in the bodies of opium-addicted mothers.

The increase in IL-10 levels among opium-addicted mothers may serve as a mechanism to counteract the elevated inflammation within their bodies. IL-10, by suppressing the release of inflammatory cytokines, helps to maintain a semblance of anti-inflammatory balance in the face of increased inflammation (Cheng & Sharma, 2015).

In a study conducted by Mardini et al. (2016), it was demonstrated that levels of IL-6 and IL-10 were elevated in the umbilical cord blood of newborns whose mothers had a history of consuming crack/cocaine during pregnancy (Mardini et al., 2016). Similarly, Fox et al. (2012) reported an increase in IL-10 levels in individuals who are addicted to cocaine (Fox et al., 2012).

In addition to cytokines, opium use during pregnancy also affected the levels of acute-phase proteins such as CRP in both maternal blood and umbilical cord blood. CRP is a well-known marker of systemic inflammation (Rizo-Téllez et al., 2023). The significantly higher levels of CRP in addicted mothers compared to the control group indicate a state of chronic inflammation. This implies that opium consumption during pregnancy can induce a persistent inflammatory state, which may have detrimental effects on both the mother and the developing fetus.

Furthermore, our study revealed elevated levels of C4 and C3 in both maternal blood and umbilical cord blood of opium-addicted mothers. These complement proteins are involved in the immune system’s defense mechanisms against pathogens (Markiewski & Lambris, 2007). However, excessive activation of complement pathways can lead to tissue damage and inflammation (Markiewski & Lambris, 2007). The higher levels of C4 and C3 observed in this study suggest that opium consumption during pregnancy may dysregulate the complement system, leading to increased inflammation in both the mother and the fetus.

Our findings demonstrated association between opium addiction and increased levels of inflammatory factors in the maternal blood. This heightened inflammatory state seemed to have a cascading effect on the developing fetus, leading to a range of neonatal complications. The presence of these inflammatory factors in umbilical cord blood suggests that they can cross the placental barrier and directly impact the fetus.

Our study revealed that mothers with a history of opium consumption exhibited higher levels of inflammatory markers postpartum compared to the control group. Nonetheless, we must consider that labor itself is an inflammatory process, which could potentially influence the observed differences in inflammatory levels. The elevated markers in the opium-consuming group might reflect a hyperresponse to the stress of labor rather than a chronic elevation due to opium consumption. The absence of mid-pregnancy sampling in our study design limits our ability to ascertain the baseline inflammatory status and to differentiate between these two scenarios.

In reviewing additional literature on the effects of opium on inflammation, we found that studies in male subjects have demonstrated that opium negatively affects immune system activity and increases inflammatory levels, suggesting a potential altered immune response in opium users (Ghazavi, Mosayebi, et al., 2013; Ghazavi, Solhi, et al., 2013). Moreover, the study by Gholamreza Asadikaram et al. (2015) provided valuable insights into the effects of opium on cytokine secretion in Jurkat cells (Asadikaram et al., 2015). The findings of increased interleukin-6 (IL-6) secretion and alterations in interferon-γ (IFN-γ) and transforming growth factor-b (TGF-β) levels post-opium exposure highlight the dysregulation of pro-inflammatory and anti-inflammatory cytokines induced by opium (Asadikaram et al., 2015).

Considering the effects of opium observed in past studies in men and in cellular model, it appears that at least part of the increase in inflammation in the opium-consuming group compared to the control group may be attributable to opium consumption. However, further research is needed to fully understand the complex relationship between opium use, the inflammatory response during labor, and long-term outcomes for both mother and child.

Opium and other opioids can increase inflammation through several mechanisms involving both the central nervous system (CNS) and the peripheral immune system (Bornavard & Fanaei, 2020; Eisenstein, 2019; Garcia et al., 2012; Ghazavi, Mosayebi, et al., 2013; Ghazavi, Solhi, et al., 2013; Liang et al., 2016; Peterson et al., 1998). These mechanisms include:

• Activation of immune cells, such as microglia and astrocytes, leading to the release of pro-inflammatory cytokines.

• Modulation of immune responses via the binding of opioids to receptors on immune cells.

• Activation of Toll-Like Receptor 4 (TLR4), leading to the production of pro-inflammatory cytokines.

These mechanisms can contribute to a state of chronic inflammation, which has been associated with various negative health outcomes, including increased susceptibility to infections and altered immune parameters (Eisenstein, 2019; Friedman et al., 2006; Garcia et al., 2012; Ghazavi, Mosayebi, et al., 2013; Ghazavi, Solhi, et al., 2013; Liang et al., 2016; Peterson et al., 1998). Understanding these pathways is crucial for developing targeted interventions to mitigate the inflammatory effects of opium use.

The impact of increased inflammation during pregnancy on the fetus and child is a critical area of research. Maternal inflammation in women addicted to opium can affect both the developing fetus and the child through several routes, (Bhagirath et al., 2021; Han et al., 2021; Kwon et al., 2022; Shimizu et al., 2023) including:

• Disruption of normal cellular processes, affecting organ formation, tissue growth, and overall health.

• Altered brain development, potentially leading to cognitive and behavioral changes in the child.

• Programming of the fetal immune system, impacting the child’s susceptibility to infections and autoimmune conditions.

In the long term, children born to mothers with chronic inflammation may have an increased risk of: (Bhagirath et al., 2021; Croen et al., 2024; Han et al., 2021; Kwon et al., 2022; Shimizu et al., 2023; Yang et al., 2021).

• Allergies, asthma, and other immune-related disorders.

• Metabolic health issues, such as obesity, diabetes, and cardiovascular diseases.

• Behavioral problems, mood dysregulation, and neurodevelopmental disorders.

Neonates exposed to opium in utero may experience Neonatal Abstinence Syndrome (NAS), characterized by withdrawal symptoms (Croen et al., 2024; McNett, 2007). NAS can affect the newborn’s well-being and require specialized care (Croen et al., 2024; McNett, 2007). Emerging literature also suggests an association between opioid exposure during pregnancy and adverse neurocognitive, behavioral, and developmental outcomes in children (Balalian et al., 2023; Wen et al., 2021). These effects may not be apparent in the neonatal period but can become more pronounced as children develop (Balalian et al., 2023; Wen et al., 2021).

In summary, maternal opium addiction and inflammation during pregnancy can have profound and lasting effects on the child’s health and development. Understanding the mechanisms underlying these effects is essential for developing effective strategies to support affected families and improve pregnancy outcomes.

Limitations and Future Directions

This study provides valuable insights into the inflammatory effects of opium consumption during pregnancy; however, there are several limitations that should be considered:

1- The inclusion criteria for the case group relied on self-reported opium consumption, corroborated by medical history. The absence of drug screening in maternal blood or urine limits the verification of the self-reported data, which could introduce bias or inaccuracies in the measurement of opium exposure.

2- Our methodology did not include the direct measurement of umbilical cord blood pH and Base Excess (BE). These parameters are critical for assessing fetal acid-base balance and oxygenation status during delivery. The increase in Neonatal Intensive Care Unit (NICU) admissions observed in our study highlights the need for these measurements to understand the full impact of opium consumption on neonatal health.

3- The study design did not include mid-pregnancy sampling, which restricts our ability to determine the baseline inflammatory status. This limitation hinders our understanding of whether part of the observed some increase in inflammation is due to labor or chronic opium consumption.

The complex relationship between opium use, the inflammatory response during labor, and long-term outcomes for both mother and child requires additional investigation. Future studies should aim to address these limitations and expand our understanding of the implications of opium consumption during pregnancy.

Conclusion

This investigation presents pioneering evidence that opium consumption during pregnancy is linked to heightened inflammatory activity in both maternal and umbilical cord blood. The study’s novel findings reveal a significant association between this inflammatory response and an escalation in neonatal complications, underscoring the potential for grave repercussions affecting both the mother and the infant. The pronounced elevation of inflammatory markers—including IL-6, IL-10, CRP, C4, and C3—points to an aberrant immune reaction triggered by opium intake. Such persistent inflammation is a critical concern for fetal development and is implicated in a spectrum of detrimental outcomes. These results underscore the urgent need for heightened awareness and preventive strategies to mitigate the risks associated with opiate exposure during the formative stages of pregnancy.

Footnotes

Acknowledgments

The authors express their gratitude to the midwives and pregnant women who participated in the study.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Zahedan University of Medical Sciences (7251).

Ethical Statement

ORCID iD

Hamed Fanaei

Data Availability Statement

The data used to support the findings of this study are available from the corresponding author upon request.*

Author Biographies

Samira Khayat, Ph.D., is an assistant professor of reproductive health and midwifery at the Pregnancy Health Research Center and Department of Midwifery, Zahedan University of Medical Sciences, Iran. She has worked as a researcher and faculty member. Her research focuses on reproductive health and pregnancy issues in vulnerable communities, including adolescents, drug addicts, and marginalized women. To date, she has conducted interventional, cross-sectional, and review studies.

Hamed Fanaei, Ph.D., is an associate professor of medical physiology at the Pregnancy Health Research Center and the Department of Physiology at Zahedan University of Medical Sciences, Iran. He is a well-experienced neuroscience and addiction scientist, with major research areas including neurodevelopment, pregnancy, behavior, and addiction.

Farideh Riki is a M.Sc. graduate in Physiology from Zahedan University of Medical Sciences, Iran. Her research interests primarily focus on the effects of addiction on pregnant women.

Shahindokht Navvabi Rigi is an assistant professor of gerontology and master of midwifery education at the Zahedan University of Medical Sciences, Iran. Her research area interest’s particular focus on women in reproductive and non-reproductive periods, caregivers and women’s aging.

Ebrahim Alijani is an Associate Professor of Medical Immunology at the Clinical Immunology Research Center and Department of Immunology at Zahedan University of Medical Sciences, Iran. His research interests primarily focus on the immune responses in human disease.

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