Treatment of Primary Fetal Hydrothorax with OK-432 (Picibanil): Outcome in 14 Fetuses and a Review of the Literature

Abstract

Background: Primary fetal hydrothorax (PFHT) is an uncommon condition with an estimated prevalence of 1 in 10,000/15,000 pregnancies. Therapeutic interventions include thoracocentesis, thoraco-amniotic shunting (TAS), and pleurodesis using OK-432. Methods: A review of the literature was performed to identify all cases of PFHT treated with TAS and OK-432. All cases of PFHT referred to the Fetal Maternal Unit at Royal Prince Alfred Hospital between 2002 and 2012 were retrospectively reviewed. In the cohort of fetuses treated with OK-432, the main perinatal outcomes evaluated were termination of pregnancy, live birth, neonatal death, and fetal death in utero. Secondary outcomes included gestational age (GA) at diagnosis, GA at treatment, GA at resolution, birth weight, and GA at birth. The development of the children was screened using the Ages and Stages Questionnaires, Version 3 (ASQ-3, 2009). Results: Primary hydrothorax was diagnosed in 31 fetuses, of which 14 had treatment with OK-432. One pregnancy terminated after treatment with OK-432. Survival was 85% (11/13): 100% in fetuses treated with OK-432 without hydrops, and 78% in those treated with hydrops. This compares well to the cases of TAS in the literature with an average survival of 63%: 85% in fetuses without hydrops and 55% with hydrops. The mean GA at birth was 36⁺⁴ weeks and mean birth weight 3,007 g. Eight of the 9 children screened with ASQ-3 scored well within the normal range. Conclusion: OK-432 appears to be a valid treatment option in fetuses with PFHT, particularly in those diagnosed at early GAs.

The utility of exome sequencing for fetal pleural effusions

“…Hydrops fetalis was reported in three independent families secondary to a genetic heterozygous variant in EPHB4 . It was further confirmed by inactivation of Ephb4 in a murine model resulting in lymphatic valve malformation . We suggest that our report, referring specifically to case 2, enhances the current literature with regard to the pathogenicity of EPHB4 variants as a cause of pleural effusions as a manifestation of hydrops fetalis.…”

“…We propose EPHB4 to be a candidate gene on the basis of prior reported associations with fetal hydrops . Hydrops fetalis was reported in three independent families secondary to a genetic heterozygous variant in EPHB4 .…”

“…In the era of personalized medicine, pleural effusions are well positioned to benefit from targeted therapies based in part on the underlying diagnosis. Some examples of personalized in utero treatment include intrauterine blood transfusion for fetal anemia, digoxin for fetal arrhythmia, steroids for cystic pulmonary airway malformations, and pleural shunt placement or intrapleural injections for chylothorax …”

Chylothorax in the neonate—A stepwise approach algorithm

“…Use of fibrin glue has been described in neonatal patients, but is mainly associated with persistent pneumothorax 96,97 . Recent reports have suggested pleurodesis with OK‐432 as an alternative therapeutic option, even in foetuses and preterm infants with bilateral pleural effusion 98–101 . Mechanical pleurodesis, without instillation of chemical agents, using only mechanical friction of the pleura, via thoracoscopy or thoracotomy, has been shown to be effective and safe in refractory chylothorax 23…”

Case Report: Pregnancy with Fetal Hydrathorax

“…The term fetal hydrothorax describes fluid accumulation in the pleural cavity area, either unilaterally or bilaterally. 1,2,3 Cases of fetal hydrothorax (FHT) are rare, with a probability of occurring in 1 out of every 10,000-15,000 pregnancies. 13,15 The incidence of primary FHT may be even higher, considering that the condition may remain undiagnosed in many cases.…”