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Prenatal Stress, Anxiety and Depression: a Mechanism Involving Crh Peptide Family.

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Upshot of prenatal exposure to maternal cortisol and psychological distress on infant development in Bengaluru, southern Republic of india: a prospective cohort study

  • Gudlavalleti Venkata Satyanarayana Murthy2,5,
  • Giridhara R. Babuone &
  • Gian Carlo Di Renzo3,4

BMC Psychiatry book 17, Article number:255 (2017) Cite this article

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Abstract

Groundwork

The mental health condition of a meaning woman and its consistent impact on foetal well being is non given much importance compared to the risk imposed past obstetric complications and medical atmospheric condition. Maternal psychological distress is a major public health problem and needs timely detection and intervention to prevent whatever adverse pregnancy consequence. There is ample evidence from literature that justifies the association of prenatal maternal mental stress and elevated cortisol with delayed infant motor and cognitive development; evidence from India being rather limited. The study aim is to prospectively appraise the association of maternal psychological distress and cortisol level with motor and cognitive development of the baby.

Methods

A sample of 2612 eligible meaning women who have been registered for antenatal care at selected public sector hospitals in Bengaluru will be recruited afterward obtaining written informed consent. They volition be assessed for the presence of maternal psychological distress in the form of depression and anxiety using advisable scales and saliva samples will be nerveless for cortisol estimation during early on, mid and late pregnancy. Follow upwards visits afterward commitment will exist washed on solar day x, 3 months, eight months and 12 months. The Bayley Scales of Infant and Toddler Development [BSID] (3rd edition) will be used to measure both motor and mental milestones in terms of Psychomotor Development Index (PDI) and Mental Development Index (MDI). Logistic regression model will be used to decide the association between the exposure variables and outcomes which will be reported as Odd'due south Ratio (OR) and 95% confidence intervals (CI).

Discussion

Our study findings could add to the growing bear witness that maternal psychological distress during pregnancy adversely influences growth and development in the offspring and subsequent development of the child. While maternal anxiety and depression can exist measured by using cocky reporting instruments, estimation of maternal endogenous cortisol levels could serve as a biomarker of prenatal psychological stress. Findings from this study could be used to focus upon the burden of mental health issues during pregnancy and to consider steps to calibration up prenatal mental health services in health intendance settings.

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Background

Pregnancy is a fourth dimension of physiologic, mental and emotional alter. Every bit a consequence, women are highly vulnerable to psychological distress that includes anxiety, low and stress [1,2,3]. During this phase of complex and dynamic changes, the fetal organs and organ systems that are forming are bailiwick to both positive and negative influences, likewise known as foetal programming [4]. There is aplenty bear witness from literature that justifies the clan of prenatal maternal stress with delayed baby motor and cognitive development wherein it has been reported that high levels of maternal stress during mid-pregnancy was significantly associated with lower scores of motor and mental evolution of the infant [5,6,7,eight].

Prenatal maternal stress has been ofttimes linked with elevated levels of maternal endogenous cortisol [nine]. The cortisol hormone plays an important role in normal development of the foetus [10]. During pregnancy, the maternal cortisol levels increase by two to four times [11]. This increase has a positive influence on neural development [12]. However, foetal exposure to excess maternal cortisol may result in impaired brain development as a result of neurotoxicity [13, fourteen]. Animal studies show that exposure to prenatal stress induced a significant ascent in maternal cortisol secretion by activating the maternal Hypothalamo Pituitary Centrality (HPA). Elevated levels of cortisol achieve the foetus and change the action of foetal HPA centrality [15,16,17]. This modification of the foetal HPA axis exerts a detrimental effect on farther growth and evolution through a series of circuitous endocrine mechanisms [18,nineteen,xx]. In animals, prenatal stress too exerts an inhibitory effect on the placental enzyme 11 β-hydroxysteroid-dehydrogenase type 2 which converts maternal cortisol to inactive cortisone resulting in a ascent in amniotic fluid cortisol level which affects foetal HPA performance [21].

The evidence of clan of prenatal stress with elevated maternal cortisol levels in humans is rather weak [22,23,24]. Nevertheless, there are few studies that accept evaluated the result of prenatal exposure to elevated maternal cortisol on infant outcomes and observed an adverse effect on infant development and lower scores of IQ in babyhood [5, 7, 25]. The timing of exposure to elevated maternal cortisol during the gestational menses appears to exist of significance. While one such study observed poor infant neuromotor evolution to be associated with exposure early in pregnancy, another one reported a pregnant association with exposure in the tertiary trimester [5, seven].

While nearly of the studies have relied on maternal self reporting of psychological distress to constitute its linkage with adverse baby outcome, at that place are a few studies in which prenatal stress did not announced to influence baby and child development [26, 27]. Thus, this kind of cocky reporting may have its own limitation in quantifying stress during pregnancy [5, 28]. Few of the studies have used both measures for establishing the presence of prenatal stress i.e., self reporting and measurement of maternal cortisol and observed an independent significant clan with agin infant and child outcomes in each case [v, seven, 29,xxx,31].

Prove from Bharat that depicts the association of prenatal stress with infant and child development is rather limited. A written report done in Goa observed the existence of a positive association between psychological morbidity during pregnancy and depression birth weight [32]. Another written report done in India establish prenatal maternal anxiety to be linked with elevated babe cortisol reactivity [33]. In some other study which was undertaken to explore the relationship between prenatal stress and babe temperament, information technology was seen that although the levels of salivary cortisol was loftier in those infants whose mothers were psychologically distressed, there was no significant association with maternal reports of baby temperament [34]. However, these studies accept not explored the effect of prenatal stress and maternal cortisol level on the mental and motor development of the offspring.

The prevalence of maternal prenatal depression has been observed to exist a little higher than 25% in depression and centre income countries [35, 36]. While core importance towards screening for obstetric risk factors and medical conditions is the norm in most settings; mental health of the pregnant women and its consequent impact on foetal well being tends to be overlooked. Maternal psychological distress is therefore a major public health problem and needs timely detection and intervention to prevent any adverse pregnancy upshot.

Given the above background, the aim of this study is to prospectively assess the association of maternal psychological distress and cortisol level with motor and cognitive development of the baby. The objectives include: (i) to depict the pattern of occurrence of maternal psychological distress during pregnancy (ii) to decide the influence of maternal psychological distress on infant motor and cognitive development (three) to determine the influence of maternal cortisol level on infant motor and cognitive evolution. (iv) to correlate maternal psychological distress with maternal cortisol levels.

The proposed hypotheses are as follows:

Hypothesis 1: Maternal self reported psychological distress is associated with adverse infant motor and cognitive evolution.

Hypothesis ii: Elevated maternal cortisol level is associated with adverse baby motor and cognitive development.

A conceptual framework of the hypothesis depicting the exposure, upshot and potential confounders is outlined in Fig. one.

Fig. one
figure 1

Conceptual Framework to depict Hypotheses 1 and 2

Full size prototype

Methods/design

Study design: Prospective cohort study

Written report participants and study setting

The study participants will include eligible meaning women attending the antenatal clinic at the Jaya Nagar general hospital, Bangalore, who fulfill the following inclusion criteria which include (i) age betwixt xviii and xl years (ii) betwixt 14 weeks to 28 weeks of gestation (iii) plan to evangelize in the study hospital (4) permanently residing in the study area within a radius of 15 km (five) total term healthy neonate with Apgar score of more than vii. Exclusion criteria will include (i) Multiple pregnancy (ii) chiliad multipara (three) major pregnancy complications: preeclampsia-eclampsia, hyperemesis gravidarum (iv) nativity complications: nevertheless births, preterm delivery, congenital anomalies (five) History of past or present intake of steroid medications.

Sample size

Evidence from literature shows that 10% to 20% of all women endure from depression or anxiety during pregnancy [37, 38]. With an expected prevalence of 15%, an allowable error of 5%, 10% variability and ability 80%, the sample size is calculated to exist 2176. Bold a driblet out charge per unit of 20%, the calculated sample size amounts to 2612.

Sampling method

All those pregnant women who are visiting the antenatal clinic will be screened for eligibility. The women who are plant to be eligible will be enlisted every month. They volition exist selected to participate in the study by means of simple random sampling, by using a serial of computer generated numbers. The selected women will exist contacted over the phone and invited to come to the study hospital. If a selected adult female denies to enter the study, the woman so with the adjacent number will be invited to participate.

Report procedures

The selected women would be recruited into the study after obtaining a written informed consent from them.

The baseline assessment will be washed at the time of recruitment between fourteen and 28 weeks (early to mid pregnancy). A. questionnaire will exist administered to collect information on socio-demographic characteristics, obstetric, medical and psychiatric past histories.

Further assessments will exist done (i) 37–38 weeks of gestation (late pregnancy), and at (ii) ten days (three) 3, eight months (iv) 12 months after birth.

A flowchart depicting the study steps is shown in Fig. two.

Fig. ii
figure 2

Flowchart depicting steps of the cohort report

Full size epitome

Measurement of study exposure and outcomes

Maternal psychological distress

The presence of maternal psychological distress will be identified by using Kessler 10 Scale of Psychological Distress (K10) for prenatal depression [39] and the ten-item Pregnancy related feet (PRA) scale for pregnancy anxiety [40]. The K10 scale is well structured and includes questions nearly feet and depressive symptoms that a person has experienced in the most recent 4 week period. Each question has five response categories ranked on a five-point scale, with the score being the sum of these responses. The PRA scale measures concerns and worries that are specific to pregnancy and childbirth. The scoring on this scale ranges from 10 to 40. These assessments will be done at (i) Baseline visit - between 14 and 28 weeks (ii) Second visit: 37–38 weeks.

The levels of the unbound cortisol hormone in blood is reliably reflected by salivary cortisol levels [41]. Maternal saliva samples will be collected for cortical analyses at (i) Baseline visit - betwixt xiv and 28 weeks (ii) Second visit: 37–38 weeks.

The salivary samples will be stored until assayed at −70 °C, in a Biorepository facility at the St. Johns Inquiry Institute. The evaluation of the samples will be done at an NABL (National Accreditation Board for Testing and Calibration Laboratories) accredited Lab. Before analysis, the samples are thawed and centrifuged for most xv min. The cortisol levels are estimated by a competitive luminescence immunoassay with a lower limit of detection of 0.5 nmol/L [42]. The baby will exist assessed at iii, 8 and 12 months for developmental indices past the Bayley Scales of Baby and Toddler Development (BSID), Third edition which measures both motor and mental milestones [43]. This will be accomplished by means of habitation visits. The Bayley scales embrace five major areas of development - cognitive, communication, concrete, socio-emotional and adaptive. The scales to measure the cognitive and physical areas of development will exist used. The weight and length of the babe will also be recorded during these visits.

All the psychometric measurement scales and BSID will be translated into the local linguistic communication 'Kannada' using the standardised WHO translation and back-translation protocol (WHO) and pre-tested before beingness finalized [44].

The Research team volition receive grooming for using these scales from a squad of experts at CSI Holdsworth Memorial Infirmary, Mysore.

Confounders

The misreckoning factors that influence the upshot variables- cortisol level and babe growth and development will be taken into business relationship at the time of information analysis. These are enlisted in Fig. 1. Information on maternal educational level, occupation, socio-economic status, pregnancy risk factors volition be obtained from the baseline information. The gestational age volition be calculated from the final menstrual catamenia every bit reported past the written report participants. Data on birth weight will be obtained from medical records. Information on breastfeeding, post-natal psychological well-being and postal service-natal depression will be collected at the 10th day visit after nascency. Maternal psychological well existence will exist assessed by using the General Wellness Questionaiire-30 which measures one'due south power for effective daily functioning [45]. This contains xxx questions which are answered on a iv- point scale. Postal service natal low will be measured past using the x-particular Edinburgh Postnatal Depression Calibration (EPDS) [46].

Data management and analysis

Data direction volition exist done using Microsoft Access which volition exist transported to SPSS Version 24 for analysis. Descriptive statistics volition be used to summarize the socio-demographic characteristics, obstetric variables, perinatal outcomes, scores obtained from measurement scales and cortisol level estimates. Confounding variables will exist tested for their relationships with the exposure (Maternal anxiety, low and salivary cortisol level) and outcome (Mental Evolution Index and Psychomotor Evolution Index) by means of correlations (Pearson correlation coefficient or Spearman rank-order correlations where appropriate) and regression analysis. Just those variables that are significantly related to the exposure and outcome will be included in further analyses. Logistic Regression Model volition be used to determine the clan between the exposure variables and outcome which will be reported as Odd's Ratio (OR) and 95% conviction intervals (CI). The statistical significance for all the tests will be causeless to be at the level of P < .05.

Ethical considerations

The protocol for the proposed study has been reviewed and approved past the institutional ethical review board (IEC) at Bengaluru campus of IIPH-H. All the study participants will be required to provide a written informed consent in the local language.

Discussion

Our study findings could add to the growing evidence that maternal psychological distress during pregnancy adversely influences growth and evolution in the offspring and subsequent development of the child. While maternal anxiety and depression can be measured past using cocky reporting instruments, estimation of maternal endogenous cortisol levels could serve as a biomarker of prenatal psychological stress. Peradventure a combination of the above mentioned subjective and objective measures could give a better measure of mental stress during the antenatal period.

The findings from this written report could be used to focus upon the burden of mental wellness problems during pregnancy with its adverse consequences and to consider steps to scale up prenatal mental health services in both public besides as private wellness settings. The written report findings could be used to plan for show based- interventions such as stress reduction programmes to reduce maternal anxiety and low during pregnancy, particularly in the Indian scenario.

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Acknowledgements

Our sincere thank you to the Department of Health and Family Welfare, Government of Karnataka for granting permission to conduct the report at Jaya Nagar General Hospital. I am grateful to Dr. Murali Krishna, a trained psychiatrist from CSI Holdsworth Memorial Infirmary,Mysore for his professional person inputs. I am also thankful to Dr. Suresh Shapeti and Mr. Ramesh for their help in facilitating administrative approvals for the written report.

Funding

The report is funded by an Intermediate Fellowship by the Wellcome Trust DBT India Alliance (Clinical and Public Health Research Fellowships).

Availability of data and materials

Requests for the datasets generated during and/or analyzed during the current study tin can be directed to the respective author. The Institutional ethics committee reviewing at IIPH-Bangalore will determine on providing the data.

Author information

Affiliations

  1. Wellcome Trust DBT Bharat Alliance Intermediate fellow in clinical and public health, Indian Institute of Public Health-Bengaluru Campus, Public Health Foundation of India, SIHFW Campus, Outset Cross, Magadi road, Bengaluru, Karnataka, 560023, India

    Anita Nath & Giridhara R. Babu

  2. Indian Establish of Public Health Hyderabad-Bengaluru Campus, S, Public Health Foundation of India, Plot # ane, Rd Number 44, Masthan Nagar, Kavuri Hills, Madhapur, Hyderabad, Telangana, 500033, India

    Gudlavalleti Venkata Satyanarayana Murthy

  3. Section of Ob/Gyn, Centre for Perinatal and Reproductive Medicine, the Midwifery School, The University of Perugia, Perugia, Italia

    Gian Carlo Di Renzo

  4. The Permanent International and European School of Perinatal, Neonatal and Reproductive Medicine, Florence, Santa Maria della Misericordia Academy Hospital, 06132 San Sisto, Perugia, Italian republic

    Gian Carlo Di Renzo

  5. International Center for Heart Health, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United kingdom

    Gudlavalleti Venkata Satyanarayana Murthy

Contributions

AN is the primary investigator of this study and is awarded the intermediate fellowship from Wellcome Trust DBT India alliance. She has conceptualized, designed and written the manuscript through all stages of preparation and submission. GVS has reviewed the application from the conceptualization phase and has contributed to each version of the manuscript. GRB has contributed to each version of the revision and participated in giving inputs in conceptualizing the paper. GCDR has critically reviewed the manuscript at each step till finalization. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Anita Nath.

Ethics declarations

Ethics approval and consent to participate

The report was reviewed and approved past the institutional ethical review board (IEC) at Bangalore campus of IIPH-H (Approval number IIPHHB/TRCIEC/118/2017), dated 31 st May 2017. Only participants willing to participate voluntarily and those who have provided written informed consent will be enrolled.

Consent for publication

Non applicable.

Competing interests

The authors declare that they accept no competing interests.

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Nath, A., Murthy, G.5.Due south., Babu, Thou.R. et al. Effect of prenatal exposure to maternal cortisol and psychological distress on infant development in Bengaluru, southern India: a prospective accomplice study. BMC Psychiatry 17, 255 (2017). https://doi.org/10.1186/s12888-017-1424-x

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Keywords

  • Pregnancy
  • Mental stress
  • Prenatal
  • Depression
  • Anxiety
  • Cortisol
  • Infant development

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