Introduction
Pre-eclampsia (Pre-E) is a serious complication of pregnancy that occurs
in approximately 5% of pregnancies in the USA [1]. Pre-E is
characterized by maternal hypertension and systemic vascular endothelial
dysfunction. Although the pathogenesis of Pre-E is not well-defined,
several studies have demonstrated that women with Pre-E have increased
circulating levels of anti-angiogenic factors such as soluble FMS-like
Tyrosine Kinase-1 (sFlt-1) [2, 3]. Infants born from mothers with
Pre-E have a reduced risk for retinopathy of prematurity, a condition
caused by excess retinal angiogenesis and neovascularization [4]. In
addition, infants born from hypertensive women have reduced skin
capillary density [5]. These observations suggest that the
anti-angiogenic milieu of pregnant women with Pre-E affects vascular
development in the fetus. Recent evidence from a murine model of the
early onset immune-mediated subtype of Pre-E suggests that the placenta
plays a key role in mediating the effects of Pre-E on fetal lung
development [6, 7].
Disruption of pulmonary vascular development is linked to impaired
alveolar growth, a hallmark feature of bronchopulmonary dysplasia (BPD).
Increased cord blood sFlt-1 is also associated with an enhanced risk of
BPD in preterm infants [8-11]. A rat model of Pre-E utilizing
intra-amniotic injection of sFlt-1 demonstrated decreased alveolar
number and reduced pulmonary vessel density at 14 days of age, which
corresponds to 1 year of human life [10]. Furthermore, a history of
maternal Pre-E is associated with increased rates of asthma, allergy,
and eczema [12, 13]. Taken together, these clinical and animal data
suggest that the effect of Pre-E on angiogenesis may affect respiratory
function in infants with Pre-E. However, there are limited data on
airway function and, to our knowledge, no data on gas transfer of
off-spring with a history of maternal Pre-E.
The objective of our study was to assess the impact of Pre-E on
respiratory outcomes in early infancy, which included lung function and
respiratory morbidity. We hypothesized that the in uteroanti-angiogenic environment of pre-E would result in impaired lung
growth and development with decreased parenchymal and airway function,
as well as increased respiratory morbidity in infants born of pregnant
women with Pre-E. To test this hypothesis, we recruited a cohort of
pregnant women with Pre-E and a cohort of normotensive pregnant women
with similar gestational ages (GA) that included preterm and term
infants. We evaluated parenchymal function with measurements of
diffusion capacity of the lung and lung volume and airway function with
measurements of forced expiratory flows. Infant pulmonary function tests
(IPFTs) were performed at approximately 6 months corrected-age, and
their respiratory status was followed through 12 months corrected age.