Fetal pulmonary artery Doppler blood flow velocity measures and early infant lung function. A prospective cohort study

Abstract

Background

Reduced lung function at birth has evident antenatal origins and is associated with an increased risk of wheezing and asthma later in life. Little is known about whether blood flow in the fetal pulmonary artery, may impact postnatal lung function.

Objective

Our primary aim was to investigate the potential associations between fetal Doppler blood flow velocity measures in the fetal branch pulmonary artery, and infant lung function by tidal flow-volume (TFV) loops at three months of age in a low-risk population. Our secondary aim was to explore the association between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries, and the same lung function measures.

Methods

In 256 non-selected pregnancies from the birth cohort study Preventing Atopic Dermatitis and ALLergies in Children (PreventADALL) we performed fetal ultrasound examination with Doppler blood flow velocity measurements at 30 gestational weeks (GW). We recorded the pulsatility index, peak systolic velocity, time-averaged maximum velocity, acceleration time/ejection time ratio, and time velocity integral primarily in the proximal pulmonary artery close to the pulmonary bifurcation. The pulsatility index was measured in the umbilical and middle cerebral arteries and the peak systolic velocity in the middle cerebral artery. The cerebro-placental ratio (ratio between pulsatility index in the middle cerebral and umbilical arteries) was calculated. Infant lung function was assessed using TFV loops in awake, calmly breathing three months old infants. The outcome was the time to peak tidal expiratory flow to expiratory time ratio (t_PTEF/t_E), t_PTEF/t_E <25^th percentile, and tidal volume per kg body weight (V_T/kg). Potential associations between fetal Doppler blood flow velocity measures and infant lung function were assessed using linear and logistic regressions.

Results

The infants were born at median (min - max) 40.3 (35.6 − 42.4) GW, with a mean (SD) birth weight of 3.52 (0.46) kg, and 49.4% were females. The mean (SD) t_PTEF/t_E was 0.39 (0.1) and the 25^th percentile was 0.33. Neither univariable nor multivariable regression models revealed any associations between fetal pulmonary blood flow velocity measures and t_PTEF/t_E, t_PTEF/t_E <25^th percentile, or V_T/kg at three months of age. Similarly, we did not observe associations between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries and infant lung function measures.

Conclusion

In a cohort of 256 infants from the general population, fetal third-trimester Doppler blood flow velocity measures in the branch pulmonary, umbilical, and middle cerebral arteries were not associated with infant lung function measures at three months of age.

Keywords:

• fetal
• Doppler
• pulmonary artery
• infant lung function
• PreventADALL
• tidal breathing

Acknowledgements

We express our gratitude to the families participating in the PreventADALL study as well as the PreventADALL study team, particularly Oda C. Lødrup Carlsen MD, Kim M. A. Endre, MD, Berit Granum, PhD, Peder Granlund, MD, Malen Gudbrandsgard, MSc, Gunilla Hedlin, MD, PhD, Torvid Kiserud, MD, PhD, Linn Landrø, MD, PhD, Live Nordhagen, MSc, Marie Nordsletten, MD, Knut Rudi, PhD, Carina M. Saunders, MD, Katrine Dønvold Sjøborg, MD, PhD, Cilla Söderhäll, Birgitte Kordt Sundet, MD, Magdalena R. Værnesbranden, MD, Johanna Wiik, MD, PhD and in memoriam Kai-Håkon Carlsen, MD, PhD.

Disclosure statement

Dr. Rehbinder received financial honoraria for lectures and presentations from Leo Pharma, Sanofi, Genzyme, AbbVie, Novartis, Norwegian Asthma and Allergy Association, and Norwegian Psoriasis and Eczema Association. No potential conflict of interest was reported by the author(s).

Additional information

Funding

Dr. Hilde and Dr. Paasche Roland received research funding from the Southeast Regional Health Authority. Dr. Hilde received financial support from the Oslo University Hospital. The PreventADALL study was financially supported by the following public funding bodies: the South-East Regional Health Authority, the Norwegian Research Council, Health and Rehabilitation Norway, Oslo University Hospital, the University of Oslo, Østfold Hospital Trust, The Foundation for Healthcare and Allergy Research in Sweden–Vårdalstiftelsen, Swedish Asthma- and Allergy Association’s Research Foundation (F2015-0047), Swedish Research Council - the Initiative for Clinical Therapy Research (921-2014-7178), Swedish Heart and Lung Foundation (20160338), Thermo Fisher Scientific, Fürst Medical Laboratory, Oslo, Norway, and by unrestricted grants from the Norwegian Association of Asthma and Allergy, the Kloster foundation, Norwegian Society of Dermatology and Venerology, and Arne Ingel’s bequest.