Amnioninfusion or expected management after midtrimester PPROM * what are the long-term effects on offspring*s general health and neurobehavioral development?

Preterm premature rupture of membranes (PPROM) before or near the limit of
viability is associated with high perinatal morbidity and mortality. Stillbirth
after an infection, abruption or cord prolapse, prematurity and respiratory
problems are the major causes of perinatal mortality and morbidity in this
group of babies.

Studies have suggested that oligohydramnios is the most important predictor of
perinatal mortality in very early PPROM and that adequate residual amniotic
fluid plays a critical role in determining either the risk for infections, such
as chorioamnionitis and neonatal infection or the prevalence of pulmonary
hypoplasia. Adequate amniotic fluid volumes might be associated with better
outcomes in pregnancies affected by very early PPROM. Locatelli et al found
that pregnancies with a median residual amniotic fluid pocket persistently less
than 2*cm were at highest risk of poor perinatal and long-term neurological
outcome while pregnancies with a pocket greater than 2*cm had significantly
better perinatal outcome (73*92% survival) and lower pulmonary hypoplasia
rates.

Serial transabdominal amnioinfusion (AI) aiming to restore the amniotic fluid
volume in pregnancies complicated by very early PPROM is an invasive procedure
which has the potential to improve the perinatal outcome. However, there is no
solid evidence to incorporate this seemingly safe procedure in daily practice.
Therefore there is the need to assess the role of amnion infusion after
midtrimester PPROM. The PPROMEXIL-III trial is designed to investigate the
effect of this intervention. The hypothesis underlying the PPROMEXIL-III trial
is that amnioninfusion will relieve oligohydramnios and therefore improve fetal
outcome by preventing pulmonary hypoplasia and neurological complications.
Furthermore, it may increase time to delivery interval, and improve fetal
biophysical profile through prevention of umbilical cord compression.

Long-term outcomes for surviving infants after amnioninfusion are rarely
reported and long-term effects on offspring*s general health, lung function and
neurobehavioral development remains unclear. Without long-term follow-up it is
impossible to determine what approach is best to manage women with midtrimester
PPROM. We therefore aim to conduct a long-term follow-up of patient*s
offspring. The long-term follow-up of the PPROMEXIL-III trial is designed to
evaluate the effect of amnioninfusion on offspring*s cognitive- and
neurobehavioral development, lung function and general health.

The long-term follow-up of the PPROMEXIL-III trial is designed to evaluate the
effect of amnioninfusion on offspring*s neurological development, lung function
and general health.

Follow-up of a multicenter randomized controlled trial (approved by METC AMC,
NL36645.081.11, NTR 3492). The long-term follow-up of the PPROMEXIL-III trial
will study the offspring of women with midtrimester PPROM and oligohydramnios
during pregnancy who have been randomized for amnioninfusion or expected
management.

Data from this follow-up study will be coupled to data of the PPROMEXIL-III
study. In the PPROMEXIL-III patients and their offspring have been asked to
attain follow-up. In the follow-up of the PPROMEXIL-III trial no further
intervention will be done. Women will be asked to fill out four questionnaires
about their children (a general questionnaire, Infant Toddler Sensory Profile
(ITSP), Emotional Assessment (ITSEA) and a questionnaire regarding respiratory
symptoms, such as asthma or other lung problems ) and a questionnaire on
quility of life afther the PPROMEXIL-III study. Furthermore, a physical
examination and a cognitive- and neurodevelopment assessment will be obtained
from these women*s offspring.

Women who participated in the PPROMEXIL-III trial will be asked to fill out
questionnaires on general health, the way their child processes sensory
information, and behaviour development of their offspring. In order to
investigate the long-term effects of the PPROMEXIL-III trial on offspring,
children born from women who participated in the PPROMEXIL-III will be
investigated in a single visit, using a neurodevelopmental assessment
(Bayley-III) and a physical examination. Participation in the follow-up trial
is not associated with risks.