Fetal umbilical, cerebral and pulmonary blood flow patterns in relation to lung function and asthma in childhood. The Generation R Study.

Background: Fetal growth restriction is associated with higher risks of childhood respiratory morbidity. Fetal blood flow adaptations might contribute to these associations. We examined the associations of fetal umbilical, cerebral, and pulmonary blood flow with wheezing patterns, lung function, and asthma in childhood. Methods: In a population-based prospective cohort study among 903 children, we measured fetal umbilical, cerebral, and pulmonary blood flow by pulsed-wave Doppler at a median gestational age of 30.3 (95% range 28.8-32.3) weeks. We obtained information about wheezing patterns until the age of 6 years by questionnaires. Lung function was measured by spirometry and information about current asthma was obtained by questionnaire at the age of 10 years. Results: Results showed a non-significant relationship between a higher umbilical artery pulsatility index (PI) and umbilical artery PI/cerebral artery PI ratio, indicating fetal blood flow redistribution at the expense of the trunk, with higher risks of early wheezing (OR [95% CI]: 2.07 (0.70-6.10) and 2.74 (0.60, 12.62) per unit increase, respectively). A higher pulmonary artery time velocity integral, indicating higher pulmonary vascular resistance, was associated with a higher risk of late/persistent wheezing (Z-score 1.14 [1.01-1.29]). A higher middle cerebral artery PI was associated with a higher FEV1/FVC (Z-score [95% CI]: 0.21 [0.01-0.42]). Results did not materially change after additional adjustment for birth and growth characteristics. Conclusion: Third-trimester fetal blood flow patterns might be related to childhood respiratory health. These findings should be considered as hypothesis generating and need further replication.