Pregnancy-Specific Stress, Fetoplacental Hemodynamics, and Neonatal Outcomes in SGA Pregnancy: Results from the PORTO Study Terri Levine, Ruth Grunau, Fiona Alderdice, Fionnuala McAuliffe, and the PORTO study team

Pregnancy-Specific Stress Fears and concerns about pregnancy Health of the fetus, labour and delivery Diet, weight gain, physical symptoms Bonding with the infant Changes in relationships with partners, friends, or family Potentially more sensitive predictor of outcomes than general prenatal stress Preterm birth, fetal behaviour, infant/child development

Fetoplacental Hemodynamics

Doppler Ultrasound Non-invasive measurement of hemodynamics Insonates arteries using a small transducer High-frequency sound bounces off blood cells passing through arteries Blood cells reflect this sound beam and change its frequency: Doppler effect

Doppler Ultrasound Outcomes Abnormal UA PI: > 95th centile for GA Abnormal MCA PI: < 5th centile for GA Indicates poor placentation, IUGR, poorer childhood developmental outcomes Fetal brain-sparing, fetal cardiovascular distress, severe fetal hypoxia and acidosis Absent end diastolic flow (AEDF) Abnormal CPR: < 1.08 (MCA PI/UA PI) Increased perinatal and neonatal morbidity and mortality, neurological sequelae, IUGR, prematurity Caesarean section, fetal distress, NICU admission, neonatal morbidity, stillbirth, poorer developmental outcomes

Prenatal Stress and Hemodynamics in Pregnancy: a Systematic Review Uterine artery (Kent 2002, Maina 2008, Mendelson 2011, Monk 2012, Teixeira 1999, Harville 2008, Helbig 2011 & 2013, Roos 2015, Vythilingum 2010) Umbilical artery (Caliskan 2009, Harville 2009, Helbig 2011, Maina 2008, Mendelson 2011, Monk 2012) Fetal MCA and CPR (Roos 2015, Sjostrom 1997, Vythilingum 2010) Umbilical vein volume blood flow (Helbig 2013) Limited evidence that prenatal stress is associated with changes in circulation Necessary improvements: larger sample sizes, repeated assessments, better control for confounders, biomarker collection, measures of pregnancy-specific stress Levine, T. A., Alderdice, F. A., Grunau, R. E., McAuliffe, F. M. Prenatal stress and hemodynamics in pregnancy: a systematic review. Archives of Women’s Mental Health 2016; 19(5): 721-739.

The PORTO Study Prospective Observational Trial to Optimise Paediatric Health in IUGR 2010-2012 7 major obstetric hospitals in Ireland and Northern Ireland 1,116 women with SGA pregnancies Serial ultrasound assessments

Eligibility Criteria Singleton pregnancies Recruited between 24+0 and 36+6 weeks’ gestation EFW < 10th percentile for gestational age No major structural or chromosomal abnormalities

Prenatal Distress Questionnaire (PDQ) 12-item self-report questionnaire about pregnancy-specific stress Sample items ‘I am worried about eating healthy foods and a balanced diet for the baby’ ‘I am anxious about labour and delivery’ ‘I am concerned that having a new baby will alter my relationship with the baby’s father’ Provides overall PDQ score and 3 factor scores Concerns about birth and the health of the baby Concerns about physical symptoms and body image Concerns about relationships and emotions

Outcomes Abnormal UA PI, AEDF, Abnormal MCA PI, Abnormal CPR Prematurity: delivery before 37 weeks’ gestation Birth weight < 2,500 grams NICU admission Composite adverse perinatal outcome Any IVH, PVL, HIE, NEC, BPD, sepsis, death

Statistical Analyses Stress measured at 3 gestational time points: Binary logistic regression Confounders included: smoking, drinking, ethnicity, BMI, mean arterial pressure, socioeconomic status, maternal age, parity NICU admission models also adjusted for prematurity Previous miscarriage not associated with pregnancy- specific stress at any time point in this sample 23-28 weeks 29-34 weeks 35-40 weeks Total Sample N = 80 N = 203 N = 213 N = 331

Abnormal Umbilical Artery PI

AEDF

Abnormal Middle Cerebral Artery PI

Abnormal Cerebroplacental Ratio

Prematurity

Birthweight < 2,500 g

NICU Admission

Adverse Perinatal Outcome

Conclusions Explored associations in women with SGA pregnancies among pregnancy-specific stress, fetoplacental hemodynamics, and neonatal outcomes Increased pregnancy-specific stress was associated with: Increased odds of abnormal MCA PI, AEDF, prematurity, birth weight < 2,500 g Decreased odds of abnormal UA PI and NICU admission No significant associations with abnormal CPR or adverse perinatal outcome

Limitations Inconsistent sample sizes at each time point Stress data not available for full PORTO cohort Low pregnancy-specific stress reported despite medical risk Nutrition, physical activity, health behaviours data not collected Highly stressed or AGA pregnancy groups not included Risk of type 1 error due to multiple comparisons

Strengths Comprehensive, time-specific exploration of pregnancy-specific stress, Doppler ultrasound parameters, neonatal outcomes Clinically useful normal/abnormal Doppler ultrasound categories Large sample sizes Repeated study design Both fetoplacental and neonatal outcomes

Thank you! Fiona Alderdice Fergal Malone Annette Burke Fionnuala McAuliffe Sean Daly Fiona Cody Ruth Grunau Michael Geary Emma Doolin Ricardo Segurado Mairead Kennelly Azy Khalid Oliver Perra Keelin O’Donoghue Cecelia Mulcahy Phyl Gargan Alyson Hunter Hilda O’Keefe Elizabeth Tully John Morrison Wendy Ooi Patrick Dicker Gerard Burke Edel Varden Fiona Lynn Amanda Ali