Abstract
A woman in her second pregnancy (G2P1), with a prior history of preterm birth at 21 weeks, had been using vaginal progesterone suppositories as prophylaxis and presented with cervical shortening and funnelling. At 24 weeks, betamethasone and nifedipine was started because of contractions. At 26 weeks, a new period of preterm contractions emerged and atosiban was added. Attempts were made to stop administration of atosiban, but every time the contractions returned. At 27 weeks the decision was made to continue atosiban and nifedipine until a gestational age of 30 weeks. At 29 weeks and 4 days she went into labour and delivered vaginally after a very short second stage. The baby weighed 1340 g with a 5-minute Apgar score of 8. The infant was admitted to the neonatal intensive care ward. On day 3, a diagnosis was made of grade IV intraventricular haemorrhage.
BACKGROUND
Tocolysis with both nifedipine and atosiban is considered a relatively harmless procedure as far as fetal-neonatal side effects are concerned. Serious fetal-neonatal side effects are not to be excluded and when no other acceptable explanation is available for intraventricular haemorrhage (IVH) an effect of the tocolytic drugs must be considered.
CASE PRESENTATION
A 30-year-old woman in her second pregnancy (G2P1), with a prior history of preterm birth at 21 weeks, presented at 23 weeks and 2 days with a shortened cervix (8 mm) and funnelling. She had been using vaginal progesterone suppositories (200 mg daily) as prophylaxis for preterm delivery.
Treatment initially consisted of home bed rest and regular follow-up. At 24 weeks she was admitted to hospital and betamethasone (2×12 mg intramuscularly) was administered and nifedipine (3×40 mg orally) was started because of contractions and dilation to 1 cm. Initially it was possible to stop labour, but at 26 weeks a new period of preterm contractions emerged and atosiban was added. Over the next few days attempts were made to stop administration of atosiban but every time the contractions returned, which gave the patient significant emotional upset. At 27 weeks the decision was made to continue atosiban and nifedipine until a gestational age of 30 weeks, although there were no further cervical changes and, hereby, we deviated from our protocol to stop atosiban after 48 hours.
At 29 weeks and 4 days she went into labour and delivered vaginally within 1 hour after the first contractions. The baby weighed 1340 g with a 5-minute Apgar score of 8. The infant was admitted to the neonatal intensive care ward. On initial evaluation, including transfontanellar ultrasound, no abnormalities were found. On day 3, a repeat transfontanellar neonatal ultrasound (as per protocol of the neonatal intensive care unit) was performed and IVH grade IV was diagnosed
OUTCOME AND FOLLOW-UP
The infant is now 2 weeks old. He is expected to have motor problems with his right arm. Further consequences remain in question.
DISCUSSION
No similar cases have been published.
As mentioned above, there are some publications addressing the relationship between various methods of tocolysis and IVH, but none pertaining to atosiban and none discussing such a lengthy administration of intravenous tocolysis.1–3
Tocolysis is generally used for short periods of time. IVH grade IV in infants over 28 weeks weighing over 1000 g are rare. The literature about the relationship between tocolysis and IVH to date reports no increased risk with the use of indomethacin and a decreased risk for magnesium sulphate—data being contradictory for ritodrine.4–6
No reports have been published addressing the relationship between atosiban and IVH. In our case, atosiban was used for a prolonged period of time. The outcome was IVH grade IV, which is unusual for a baby this age and size. No data are available on the effect of combination tocolysis on such outcome measures as IVH. We speculate that some activity of atosiban on the vasopressin receptor, especially when used for a prolonged period of time, might cause changes in cerebral vascular tone, increasing the risk for IVH when withdrawn.
LEARNING POINTS
It is as yet unknown what harmful effects, if any, prolonged tocolysis with atosiban can have on neonatal outcome.
No large study has been done to assess the relationship between atosiban and intraventricular haemorrhage.
When considering long-term tocolysis remember the possibility of as yet unknown effects on the neonate.
Footnotes
Competing interests: none.
Patient consent: Patient/guardian consent was obtained for publication.
REFERENCES
- 1.Harris NJ, Palacio D, Ginzel A, et al. Are routine cranial ultrasounds necessary in premature infants greater than 30 weeks gestation? Am J Perinatol 2007; 24: 17–21 [DOI] [PubMed] [Google Scholar]
- 2.Köksal N, Baytan B, Bayram Y, et al. Risk factor for intraventricular haemorrhage in very low birth weight infants. Indian J Pediatr 2002; 69: 561–4 [DOI] [PubMed] [Google Scholar]
- 3.Weintraub Z, Solovechick M, Reichman B, et al. Effect of maternal tocolysis on the incidence of severe periventricular/intraventricular haemorrhage in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2001; 85: F13–7 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Gleissner M, Jorch G, Avenarius S. Risk factors for intraventricular hemorrhage in a birth cohort of 3721 premature infants. J Perinat Med 2000; 28: 104–10 [DOI] [PubMed] [Google Scholar]
- 5.Vermillion ST, Newman RB. Recent indomethacin tocolysis is not associated with neonatal complications in preterm infants. Am J Obstet Gynecol 1999; 181: 1083–6 [DOI] [PubMed] [Google Scholar]
- 6.Palta M, Sadek M, Lim TS, et al. Association of tocolytic therapy with antenatal steroid association and infant outcomes. Newborn Lung Project. Am J Perinatol 1998; 15: 87–92 [DOI] [PubMed] [Google Scholar]
