Antenatal Stress and Infants In MAR (SARA)

The Effects of Antenatal Stress on the Newborn in Medically Assisted Reproduction: the SARA Study

The goal of this observational longitudinal study is to examine the association between prenatal psychological and biological stress and neonatal health outcomes in couples who conceived through medically assisted reproduction. The study includes expectant mothers and fathers during pregnancy and at birth and focuses on pregnancies achieved through homologous fertilization and heterologous fertilization via oocyte donation.

The main questions this study aims to answer are:

1. How do psychological and biological indicators of stress manifest during pregnancy in women who have undergone medically assisted reproduction?
2. Is prenatal maternal stress associated with neonatal health outcomes independently of genetic factors?
3. How does perceived stress present in expectant fathers during pregnancy? Researchers will compare couples who conceived through homologous fertilization with couples who conceived through heterologous fertilization via oocyte donation to understand whether associations between prenatal maternal stress and neonatal outcomes are independent of shared genetic background.

Participants will:

• Complete a remote eligibility assessment collecting information on pregnancy characteristics, parental health, and maternal psychological well-being
• Complete online questionnaires at multiple time points during pregnancy and at birth assessing anxiety and depressive symptoms, perceived social support, and self-efficacy (both parents), as well as pregnancy-specific measures and prenatal bonding (mothers only)
• In late pregnancy, mothers will collect saliva samples at home over two consecutive days to assess biological markers of stress (cortisol and alpha-amylase)

Study Overview

• Status: Recruiting
• Conditions: Pregnancy and Medically Assisted Reproduction
• Intervention / Treatment: Other: Diagnostic procedures

Detailed Description

This observational, longitudinal, and multidisciplinary study investigates how prenatal psychological and biological stress affects neonatal outcomes in couples who conceived through medically assisted reproduction. The study employs a cross-fostering design, comparing mother-infant diads who are genetically related with those who are not. This allows researchers to distinguish the effects of prenatal stress from genetic influences. Data from this study may also be compared with findings from a previous study by our research group ("EDI Study"; Nazzari et al., 2019, 2020a, 2020b) for common objectives. The study is non-commercial and conducted on a not-for-profit basis.

Participants are recruited through fertility centers, where physicians present the study to prospective parents during routine visits, supported by brochures and informational materials.

Mothers undergo an initial screening using the Quick SCID-5 to exclude psychiatric disorders other than anxiety and depression, and complete a health questionnaire to assess physical status during pregnancy.

Eligible mothers and fathers then participate in several phases of data collection throughout pregnancy and at birth. Both parents complete online questionnaires assessing anxiety, depressive symptoms, perceived social support, and general self-efficacy. Mothers additionally complete pregnancy-specific measures, including the NuPDQ to evaluate prenatal distress and the Pre EA-SR to assess prenatal emotional availability and bonding with the fetus. In the third trimester, mothers also collect saliva samples at three points during the day across two consecutive days to measure stress-related biological markers (cortisol and alpha-amylase).

At birth, neonatal outcomes-including gestational age, weight, length, head circumference, and any perinatal complications-are recorded. Mothers also provide information about the impact of medically assisted reproduction on daily life and the psychological support they received during pregnancy.

The enrollment period for each participant lasts approximately 8 months, from recruitment in the first two months of pregnancy until childbirth. The overall study duration is 36 months.

Data analysis will employ multiple regression and hierarchical linear models to account for both primary and secondary outcomes and handle missing data appropriately.

This study will provide valuable insights into how prenatal stress manifests behaviorally, psychologically, and physiologically in parents who have undergone assisted reproduction and how it relates to neonatal outcomes. Findings could inform early interventions to support families in these populations from the very first stages of pregnancy.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Alessandra Frigerio, PhD; Phone Number: +39031877595; Email: alessandra.frigerio@lanostrafamiglia.it
• Study Contact Backup: Name: Simone Forni; Phone Number: +39031877111; Email: simone.forni@lanostrafmiglia.it

Study Locations

• Italy
  • Bergamo
    • Bergamo, Bergamo, Italy, 24127
      • Recruiting
      • Ospedale Papa Giovanni XXIII
      • Contact: Head of the Assisted Reproduction Unit, MD; Phone Number: +39035267111; Email: ffusi@asst-pg23.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Couples from Lombardy, Italy, who conceived through medically assisted reproduction are recruited via fertility centers. The study includes first-trimester pregnant women and their male partners with singleton pregnancies.

Description

Inclusion Criteria:

• Pregnant women in the first trimester and their respective partners.
• Pregnancy achieved through homologous assisted reproduction techniques.
• Pregnancy achieved through heterologous assisted reproduction via oocyte donation.
• Singleton pregnancy.
• Pregnancy achieved through FIVET techniques.

Exclusion Criteria:

• Parents under 18 years of age.
• Pregnancy achieved through heterologous assisted reproduction via donor sperm.
• Pregnancy achieved without FIVET techniques.
• Maternal hypertension during pregnancy.
• Endocrine or immune system disorders during pregnancy.
• Chronic use of medications during pregnancy (including anti-inflammatory drugs, antidepressants, or steroids).
• Alcohol or substance abuse.
• Smoking during pregnancy.
• Psychiatric disorders other than anxiety or depression.
• Pregnancy or perinatal complications.
• Multiple pregnancy (twins or higher-order multiples).
• Preterm birth (before 35 weeks of gestation).
• Health problems in the newborn at birth.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Homologous fertilization group; Mother shares genetic heritage with the child	Other: Diagnostic procedures; psychological and biological multimodal assessment of stress
Heterologous fertilization group; Mother does not share genetic heritage with the child (oocyte donation)	Other: Diagnostic procedures; psychological and biological multimodal assessment of stress

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal Anxiety	Levels of anxiety in mothers during pregnancy and at birth, measured using the STAI	Assessed in the 1st trimester (11th-13th week), 2nd trimester (22nd-24th week), 3rd trimester (34th-36th week), and at birth.
Maternal Depression	Levels of depressive symptoms in mothers during pregnancy and at birth, measured using the EPDS	Assessed in the 1st trimester (11th-13th week), 2nd trimester (22nd-24th week), 3rd trimester (34th-36th week), and at birth.
Maternal salivary cortisol	Salivary cortisol levels measured at three time points across two consecutive days in late pregnancy, reflecting HPA axis	3rd trimester (34th-36th week of pregnancy)
Maternal salivary alpha amylase	Salivary alpha-amylase levels measured at three time points across two consecutive days in late pregnancy, reflecting sympathetic nervous system activity.	3rd trimester (34th-36th week of pregnancy).
Paternal Anxiety	Levels of anxiety during pregnancy and at birth measured using the STAI	1st trimester (11th-13th week), 2nd trimester (22nd-24th week), 3rd trimester (34th-36th week), and at birth
Paternal depression	Levels of depressive symptoms in fathers during pregnancy and at birth, measured using the EPDS	1st trimester (11th-13th week), 2nd trimester (22nd-24th week), 3rd trimester (34th-36th week), and at birth.
Neonatal Outcomes	Gestational age, birth weight, length, head circumference, and any perinatal complications recorded at birth.	At birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy-Specific Distress (maternal)	Levels of pregnancy-related stress assessed using the NuPDQ questionnaire	1st trimester (11th-13th week), 2nd trimester (22nd-24th week), 3rd trimester (34th-36th week)
Prenatal Emotional Availability	Quality of the mother's emotional availability and bonding with the fetus, measured using the Pre EA-SR questionnaire	1st trimester (11th-13th week), 2nd trimester (22nd-24th week), 3rd trimester (34th-36th week)
Perceived Social Support	Parental perception of support from family, friends, and significant others, measured using the MSPSS questionnaire.	1st trimester (11th-13th week), 2nd trimester (22nd-24th week), 3rd trimester (34th-36th week), and at birth.
Parental Self-Efficacy	General sense of self-efficacy assessed in both parents using the GSE questionnaire	1st trimester (11th-13th week), 2nd trimester (22nd-24th week), 3rd trimester (34th-36th week), and at birth.
Infertility-Related Experiences and Psychological Support	Maternal report on the impact of medically assisted reproduction on daily life and the psychological support received, collected via an ad hoc questionnaire	3rd trimester (34th-36th week

Collaborators and Investigators

• Sponsor: IRCCS Eugenio Medea
• Collaborators: A.O. Ospedale Papa Giovanni XXIII

Publications and helpful links

General Publications

• Lobel M, Cannella DL, Graham JE, DeVincent C, Schneider J, Meyer BA. Pregnancy-specific stress, prenatal health behaviors, and birth outcomes. Health Psychol. 2008 Sep;27(5):604-15. doi: 10.1037/a0013242.
• Yang Z, Wang X, Wang M, Yan S, Wu F, Zhang F. Trajectory of prenatal anxiety and depression and its association with fetal growth development. Early Hum Dev. 2023 Dec;187:105875. doi: 10.1016/j.earlhumdev.2023.105875. Epub 2023 Oct 17.
• Salevaara M, Punamaki RL, Unkila-Kallio L, Vanska M, Tulppala M, Tiitinen A. The mental health of mothers and fathers during pregnancy and early parenthood after successful oocyte donation treatment: A nested case-control study. Acta Obstet Gynecol Scand. 2018 Dec;97(12):1478-1485. doi: 10.1111/aogs.13421. Epub 2018 Aug 6.
• Rice F, Harold GT, Boivin J, van den Bree M, Hay DF, Thapar A. The links between prenatal stress and offspring development and psychopathology: disentangling environmental and inherited influences. Psychol Med. 2010 Feb;40(2):335-45. doi: 10.1017/S0033291709005911. Epub 2009 May 29.
• Nazzari S, Fearon P, Rice F, Dottori N, Ciceri F, Molteni M, Frigerio A. Beyond the HPA-axis: Exploring maternal prenatal influences on birth outcomes and stress reactivity. Psychoneuroendocrinology. 2019 Mar;101:253-262. doi: 10.1016/j.psyneuen.2018.11.018. Epub 2018 Nov 14.
• Mascarenhas M, Sunkara SK, Antonisamy B, Kamath MS. Higher risk of preterm birth and low birth weight following oocyte donation: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2017 Nov;218:60-67. doi: 10.1016/j.ejogrb.2017.09.015. Epub 2017 Sep 19.
• Gilles M, Otto H, Wolf IAC, Scharnholz B, Peus V, Schredl M, Sutterlin MW, Witt SH, Rietschel M, Laucht M, Deuschle M. Maternal hypothalamus-pituitary-adrenal (HPA) system activity and stress during pregnancy: Effects on gestational age and infant's anthropometric measures at birth. Psychoneuroendocrinology. 2018 Aug;94:152-161. doi: 10.1016/j.psyneuen.2018.04.022. Epub 2018 Apr 22.
• Garcia-Blanco A, Diago V, Hervas D, Ghosn F, Vento M, Chafer-Pericas C. Anxiety and depressive symptoms, and stress biomarkers in pregnant women after in vitro fertilization: a prospective cohort study. Hum Reprod. 2018 Jul 1;33(7):1237-1246. doi: 10.1093/humrep/dey109.
• Caparros-Gonzalez RA, Romero-Gonzalez B, Quesada-Soto JM, Gonzalez-Perez R, Marinas-Lirola JC, Peralta-Ramirez MI. Maternal hair cortisol levels affect neonatal development among women conceiving with assisted reproductive technology. J Reprod Infant Psychol. 2019 Nov;37(5):480-498. doi: 10.1080/02646838.2019.1578949. Epub 2019 Feb 27.
• Bolten MI, Wurmser H, Buske-Kirschbaum A, Papousek M, Pirke KM, Hellhammer D. Cortisol levels in pregnancy as a psychobiological predictor for birth weight. Arch Womens Ment Health. 2011 Feb;14(1):33-41. doi: 10.1007/s00737-010-0183-1. Epub 2010 Sep 25.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: February 5, 2026
• First Submitted That Met QC Criteria: February 5, 2026
• First Posted (Actual): February 13, 2026

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: salivary cortisol; salivary alpha amylase; antenatal depression; antenatal anxiety; medically assisted reproduction
• Other Study ID Numbers: 222/24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No