Reversible fetal hydrops associated with indomethacin use

Pratt, Leslie; DiGiosia, Juliana; Swenson, Jeanine; Trampe, Barbara; Martin, Chester B.

doi:10.1016/s0029-7844(97)00392-x

Cited by 14 publications

(7 citation statements)

References 7 publications

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“…Maternal side effects include the prolongation of pregnancy and labor [6,7]. Reported adverse fetal side effects of indomethacin and other NSAIDs include constricted ductus arteriosus (DA) [3,[8][9][10][11][12], limb ischemia [13], hydrops fetalis [14,15], oligohydramnios, ileal perforation [16], and cystic brain lesions [17]. The possible teratogenic effects of NSAIDs used in early pregnancy include gastroschisis, associated with aspirin and ibuprofen [3,11].…”

Section: Introductionmentioning

confidence: 99%

Effect of Diclofenac Sodium Administration during Pregnancy in the Postnatal Period

Gökçimen¹,

Aydin²,

Karaöz³

et al. 2001

Fetal Diagn Ther

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Objective: The present study aimed to investigate the possible postnatal effects on the liver, kidney and testicular tissues of the offspring of rats given diclofenac sodium (DS) during pregnancy. Methods: At the beginning of the experiment, 80 rats (20 males and 60 females) were raised together for mating purposes. At the end, 50 pregnant rats were obtained and used as the experimental subjects. All pregnant rats were divided into 2 groups, each with 25 rats. The rats of the control group received physiological serum, 1 cm³/kg live weight per day, and the rats of the treatment group were injected with DS, 1 mg/kg live weight per day from the 5th to the 20th day of pregnancy. Four weeks after birth, tissue samples were obtained under anesthesia by perfusion fixation from a total of 40 offspring, 20 (10 males, 10 females) from the control group and 20 (10 males 10 females) from the DS group. Paraffin sections were dyed with hematoxylin eosin and examined under light microscopy. Results: The gestation period was significantly prolonged with DS-treated rats (p < 0.001). A moderate significant enlargement in the periportal area (p < 0.05), sinusoidal dilatation (p < 0.001), bile duct proliferation (p < 0.001), pyknosis in the nucleus of hepatocytes, and vacuolar degeneration in parenchymal cells (p < 0.001) were observed in DS-treated rats. Morphological changes in the liver were found to be similar both in female and male rats. Under light microscopy a similar morphological structure was observed in the kidney and testicular tissues of both the DS-treated and control rats. Conclusion: Significant morphological changes were observed in the livers of the offspring whose parents had been treated with DS. No significant differences were observed in liver morphology between the female and male offspring. There were no significant effects of DS on the morphology of the kidney and testis in all offspring.

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Section: Introductionmentioning

confidence: 99%

Effect of Diclofenac Sodium Administration during Pregnancy in the Postnatal Period

Gökçimen¹,

Aydin²,

Karaöz³

et al. 2001

Fetal Diagn Ther

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“…Although several studies indicate that fetal ductal constriction following indomethacin treatment is usually reversible after cessation of the treatment, we hypothesize that in our case the heart had been overworked from the high‐output state and was too vulnerable to tolerate the extra afterload caused by indomethacin‐induced ductal closure, resulting in rapid development of cardiac failure and frank hydrops fetalis.…”

Section: Discussionmentioning

confidence: 74%

Hemodynamic assessment of indomethacin‐induced fetal heart failure in high‐output state

Tongsong

Luewan

Srisupundit

et al. 2013

J of Clinical Ultrasound

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Hemodynamic study was performed on a 32-year-old woman presenting at 27 weeks' gestation. Ultrasound revealed a single normal fetus with mild cardiomegaly, polyhydramnios, and placental chorioangioma. Doppler study showed increased middle cerebral artery peak systolic velocity, normal Tei index, and forward flow of "a" wave with normal preload in the ductus venosus. Twelve hours after initiation of indomethacin for tocolysis, frank hydrops fetalis developed rapidly. The right ventricle showed poor contractility and performance. Markedly increased preload in ductus venosus with reversed "a" wave and pulsations in the umbilical vein were demonstrated. This study suggests that indomepacin treatment in fetal high-cardiac output state should be used with extreme caution.

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“…Diastolic and global function: Not assessed. Systolic dysfunction: All NSAIDs increased the PSV in the ductus arteriosus, indicating constriction which might also cause tricuspid regurgitation [17,28,35]. Furthermore, one of the two studies found decreased right ventricular fractional shortening probably associated with an increased ventricular inner end-diastolic diameter (Figure 2) [14,28].…”

Section: Nonsteroidal Anti-inflammatory Drug (Nsaid)mentioning

confidence: 99%

Drug exposure during pregnancy and fetal cardiac function – a systematic review

Kolding

Eken

Uldbjerg

2020

Journal of Perinatal Medicine

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Background:The aim of this systematic review was to describe the effects of drug exposure during pregnancy on fetal cardiac function. Methods: We searched MEDLINE, Embase, Cochrane and SCOPUS for studies assessing fetal cardiac function in drug-exposed human pregnancies. Risk of bias was assessed by the Risk Of Bias In Non-randomized Studies of Interventions (ROBIN-I) tool. Results: We included 32 studies on eight different drug groups. They included 51 outcome variables, which were all based on ultrasound techniques primarily assessing systolic function: pulsed wave Doppler, tissue Doppler imaging (TDI), and B-and M-mode. Overall, the risk of bias was moderate. β 2 agonists increased the systolic velocity in the ductus arteriosus and the fetal heart rate. β-blockers caused unchanged or decreased systolic velocity of the pulmonary trunk. Corticosteroids increased the velocity in the ductus arteriosus. Furthermore, in growth-restricted fetuses with an increased myocardial performance index (MPI′) on the right side, corticosteroids normalized this variable. Nonsteroidal anti-inflammatory drugs (NSAIDs), but not acetylsalicylic acid, increased the flow velocities in the ductus arteriosus, decreased the shortening fraction and increased the end-diastolic ventricular diameters. Metformin and insulin normalized the diastolic strain and global longitudinal strain in diabetic pregnancies. Highly active antiretroviral therapy (HAART) exposure increased the E/A ratio on the right side, prolonged the isovolumic relaxation time (IRT) and ejection time, shortened the isovolumic contraction time (ICT), and decreased left myocardial systolic peak velocities. Chemotherapy did not cause detectable changes. Conclusion: Six of the eight drug groups caused detectable changes in fetal cardiac function. However, the evidence was hampered by only a few studies for some drugs.

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Reversible fetal hydrops associated with indomethacin use

Abstract: Ultrasonographic screening for signs of constriction of the ductus arteriosus should be done within 48 hours of instituting indomethacin therapy at any gestational age.

Cited by 14 publications

References 7 publications

Effect of Diclofenac Sodium Administration during Pregnancy in the Postnatal Period

Effect of Diclofenac Sodium Administration during Pregnancy in the Postnatal Period

Hemodynamic assessment of indomethacin‐induced fetal heart failure in high‐output state

Drug exposure during pregnancy and fetal cardiac function – a systematic review

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