Preterm birth, defined as birth occurring prior to 37 completed weeks, is a worldwide health issue with a marked difference in prevalence between developed and developing countries. The global prevalence of preterm birth is 9.6 percent. The rate of preterm birth in Pakistan is 15.7 percent, whereas it is 6.6 percent in Australia. Preterm birth is one of the major contributors to infant mortality and morbidity. Given the high prevalence of psychological disorder in women during pregnancy, it is important to understand the relationship between psychosocial risk factors and preterm birth.
Antenatal depression is common during the second and third trimesters with a systematic review showing point estimates and 95 percent confidence intervals of 12.8 percent and 12 percent, respectively. In contrast, point prevalence of 25 percent was identified in the third trimester of pregnant women residing in a rural sub-district of Pakistan. Pakistani pregnant women may be particularly vulnerable to stress as women’s health needs are not given priority. Additionally, changes in family systems, specifically structures and practices, and values attached to birth of a male child may create unique social pressures that may influence mental health. Consequently, there is a need to understand psychosocial risk and their relationships to preterm birth that may be unique for Pakistani women.
The etiologic contribution of psychosocial processes during pregnancy and preterm birth remain elusive as findings of studies examining the association between stress or depression and preterm birth have not been consistent. Although many studies demonstrate an association, others suggest that racial disparity is an underlying factor. The varied concepts and models and tools used to define stress (negative life events, perceived stress, subjective feelings of anxiety, daily hassles) and depression (thought patterns, symptoms of depression) contribute to the lack of clarity about the association between psychosocial characteristic factors and preterm birth. Cortisol, which is referred to as the ‘stress hormone’, is activated in response to stress and depression and can be measured in blood, saliva or urine. Consequently, cortisol levels may be a more objective measure of stress and depression, and thereby facilitate our understanding of the relationship between stress, depression and preterm birth.
Studies undertaken in South Asia have examined the contribution of maternal factors like maternal education, age, parity, birth interval and antenatal visit on preterm birth. However, none of these studies have considered maternal stress or cortisol in relation to preterm birth. We aimed to determine the relationship between maternal stress, depression, cortisol levels and preterm birth in pregnant women in Karachi. Our hypotheses were: there is a positive relationship between maternal stress and depression during pregnancy and cortisol level; there is a positive relationship between cortisol level and preterm birth; there is a positive relationship between maternal stress and depression during pregnancy and preterm birth; and there is a positive relationship between maternal depression and stress during pregnancy.
We enrolled all consenting pregnant women between 18 and 40 years of age with 28 to 30 weeks of gestation based on their last menstrual period (LMP) and planned to deliver at the same hospital – the Aga Khan Hospital for Women and Children at Kharadar and Karimabad.
Pregnancy outcome and delivery information, including gestational age at birth, was obtained from the medical records and the postpartum wards of both the centres. Preterm birth was defined as birth occurring prior to 37 completed weeks, while term birth was defined as birth between 37 and 42 weeks.
RESULTS: One hundred eight seven pregnant women were assessed for eligibility, of which 172 were eligible. One hundred twenty five pregnant women completed both the questionnaire and a cortisol level. Seven women provided only questionnaire data. Hence, data from 125 pregnant women contributed to the analysis when relationships included cortisol, and data from 132 pregnant women contributed to the analysis when the relationship did not include cortisol (relationship between stress and depression and preterm birth, and stress and depression). Twenty six of the pregnant women were found to have a high level of stress and 54 reported antenatal depression. Fifteen births were preterm. Cortisol level was measured as a continuous variable; however, data were not normally distributed.
There was no evidence of a positive relationship between either stress and cortisol or between maternal depression and cortisol levels. There was no significant difference in cortisol levels of mothers with preterm infants and those with full term infants. There was no significant difference between maternal stress during pregnancy and preterm birth or between maternal depression during pregnancy and preterm birth. A significant positive relationship was identified between stress and depression.
In the invariable logistic regression analysis, cortisol level, stress or depression were not associated with preterm birth. Preterm birth was associated with higher parity, past delivery of a male infant and higher levels of paternal education.
DISCUSSION: Rates of stress (19.7 percent) and depression (40.9 percent) in pregnant Pakistani women in this study are high. Our findings are consistent with a rate of 39.4 percent among Pakistani women residing in Karachi, but lower than the rate of 18 percent reported by others.
Ethnic differences in biological responses (hypothalamic-pituitary-adrenal [HPA] axis and placenta) may explain the discrepancy in the reported cortisol concentrations. In the present study, verification was requested for all cortisol levels which were reported to be high.
We identified a strong positive significant relationship between maternal stress and depression. The findings of this study, therefore, support the construct that there is a positive relationship between maternal depression and stress. Studies examining the relationship between stress and pregnancy outcomes, and/or depression, and pregnancy outcomes have asserted that there is an independent relationship to pregnancy outcomes.
We found no relationship between maternal stress and cortisol level.
The findings of this study may be explained by allostatic load that distinguishes between acute and chronic stress and suggests how chronic stress affects the hormonal, immune and physiologic response in the body. In situations of short-term or acute stress, the body regains homeostasis, whereas with exposure to long term or chronic stress, the body does not regain homeostasis and allostatic load is elevated that activates the HPA and the autonomic nervous system (corticotrophin-releasing-hormone, adrenocorticotropic hormone, cortisol, catecholamine, cytokines) to potentially increase the risk of preterm birth. A study exploring a threshold model suggested that stress beyond a certain level affects the relationship between stress and depression. In the present study, the stress tool measured cumulative stress and did not differentiate between acute and chronic stress that may have influenced the findings. In addition, stress, depression and cortisol levels were measured at a single point in time, which may be inadequate for understanding the complex relationship between acute and chronic stress, depression and cortisol levels.
We found no relationship between maternal depression and cortisol levels, which is in contrast to several studies, which report higher cortisol levels in depressed women. In this study, blood samples were used to measure cortisol levels, whereas the other studies used first morning or midmorning urine samples, which may have influenced the findings. A 24-hour urine collection must be obtained to acquire a more accurate measure of cortisol level, as it is a “useful index of integrated 24 hours plasma free cortisol”. The role of depression as an activator of the HPA axis compared to other co-morbid factors, such as anger and anxiety, is unclear, and would perhaps influence cortisol levels.
There was no relationship between cortisol levels and preterm birth. Only a small number of women experienced preterm birth and these small sample sizes increase the likelihood of making a type II error.
Our study did not reveal any relationship between cortisol, stress and depression assessed at 28 to 30 weeks. However, studies assessing the relationship earlier in gestation have demonstrated relationships between some of these variables. Consequently, differences in time points of assessment may explain why our findings are inconsistent.
In our study, increased parity was identified as a risk factor for preterm birth, and it has been proposed that physiologic risk factors common in multiparous women (placenta previa, placental abruption, postpartum haemorrhage) may partly explain the higher risk of preterm birth. The literature is contradictory with some studies demonstrating an association between increased parity and preterm birth, while others showing no association. A systematic review revealed no association between grand multiparity and great grand multiparity and preterm birth. The role of parity may be context specific, with effects of poverty combined with stress, and other factors associated with preterm birth (age, education and ethnicity) interacting in unique ways to increase risk of preterm birth in Pakistani women.
We found that preterm birth was associated with prior delivery of a male child. The proportion of male infants is higher among preterm births and this pattern is evident in different populations. Pakistan has a high rate of preterm birth and since boys are more likely to be born preterm, it is plausible that the male children at home were born preterm. The risk of preterm birth in the next pregnancy is about 15 percent to more than 50 percent. Consequently, this may explain the association between male child at home and preterm birth in this study. We did not collect data on the gestational age of the male child at home; thus, we cannot confirm this premise.
We found that higher levels of paternal education reduced the risk of preterm birth. Education has been used as a proxy for socioeconomic status. Studies from industrialised countries demonstrate an association between socioeconomic inequalities (low education level of women) and preterm birth. In Pakistan, gender inequality in education is evident from differences in literacy rates: adult male literacy rate is 43 percent, whereas adult female literacy rate is 28 percent. Our study sample was more educated than the general population, with 60.5 percent of the husbands and 50 percent of the pregnant women disclosing they had a baccalaureate or higher degree. The education level of the husband may combine with other indicators of socioeconomic status (occupational status) and psychosocial factors (decision making authority of women) to reduce the risk of preterm birth or the finding may simply be due to chance.
Women with medical or obstetrical histories were excluded from this study, and limitations in medical records and poor health literacy of the mothers precluded classification into the other two subtypes of preterm birth – spontaneous preterm labour without premature rupture of chorioamniotic membranes (PROM), and preterm PROM with vaginal or caesarean section delivery. Examining the subtypes of preterm birth may permit consideration of the etiological heterogeneity of preterm birth; though, this view remains contentious given the similar processes leading to preterm birth. A study examining maternal risk factors in a hospital-based cohort of black and white women in relation to subtypes of preterm birth found differences in set of risk factors associated with medically indicated preterm. However, similarities were reported in set of risk factors in the other two subtypes; although, differences were noted in effect size of specific risk factors. The authors concluded that grouping preterm birth into spontaneous and medically indicated preterm birth was appropriate given the current state of evidence.
The sample of this study was not completely representative of women in Karachi, thereby impacting the external validity of the study. Of the 187 women, 81 had an ultrasound done in the first trimester and 55 had an ultrasound in the second trimester; however, all pregnant women had their LMP recorded in their patient chart. Although earlier ultrasound (in the first trimester) provides better pregnancy dating than ultrasound in the second trimester, to ensure a consistent approach in dating pregnancy, the LMP was used to determine gestational age. We measured stress, depression and cortisol levels at a single point in time and within a two-week timeframe that provides a very limited assessment of the psychosocial health of the pregnant women throughout the pregnancy.
A longitudinal cohort study, with multiple measures of stress, depression and cortisol levels, as well as measures of anxiety and other stress hormone biomarkers may add new knowledge and enhance our understanding about the relationship between stress, depression, anxiety, cortisol levels and preterm birth. Lastly, in the present study, only 15 women experienced preterm birth, which should be considered in interpreting the findings.
CONCLUSION: Preterm birth was associated with higher parity, past delivery of a male infant and higher levels of paternal education. There was no relationship between maternal stress and depression, cortisol and preterm birth when assessed cross-sectionally at a single point in gestation. A larger longitudinal cohort study, with multiple measures of stress, depression and cortisol levels, as well as a measure of anxiety may add new knowledge and enhance our understanding about the relationship between stress, depression, anxiety, cortisol levels and preterm birth. There were high rates of stress and depression among this sample suggesting that there are missed opportunities to address mental health needs in the prenatal period in Pakistan. Improved methods of measurement are required to better understand the psychobiological basis of preterm birth.
Extracted from Kiran Shaikh, Shahirose S Premji, Marianne S Rose, Ambreen Kazi, Shaneela Khowaja and Suzanne Tough’s research paper titled ‘The association between parity, infant gender, higher level of paternal education and preterm birth in Pakistan: a cohort study’.