Outcome of Very Low Birth Weight Infants Exposed to Antenatal Indomethacin for Tocolysis

Doyle, Nora M.; Gardner, Michael O.; Wells, Lorraine; Qualls, Clifford; Papile, Lu-Ann

doi:10.1038/sj.jp.7211256

Cited by 20 publications

(15 citation statements)

References 24 publications

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“…Similar to other studies, 11,13,16,[19][20][21] we found that the neonatal outcomes among antenatally exposed and non-exposed ELBW infants were similar. More importantly, the incidence of adverse neonatal events in our study is similar to that of other populations of comparable GA who had not been exposed to antenatal indomethacin.…”

Section: Discussionsupporting

confidence: 91%

The effects of indomethacin tocolysis on the postnatal response of the ductus arteriosus to indomethacin in extremely low birth weight infants

et al. 2006

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Background: Antenal indomethacin reportedly decreases the responses of a symptomatic patent ductus arteriosus (sPDA) to postnatal indomethacin treatment. Whether a similar exposure affects the responses to indomethacin prophylaxis is unknown.Objective: To evaluate the clinical responsiveness of ductus arteriosus to indomethacin prophylaxis and to the treatment of sPDA in extremely low birth weight (ELBW) infants following indomethacin tocolysis.Methods: Retrospective cohort study of 58 ELBW infants whose mothers received indomethacin tocolysis (study) and 58 ELBW infants whose mothers did not (controls), matched by gender, gestational age (GA), birth weight and postnatal sPDA management (prophylaxis or early treatment).Results: Indomethacin was used as a tocolytic at a median dose of 250 mg, for a duration of 2 days, and ending 1 day before delivery. Study and control mothers were comparable in demographics, antenatal steroid use, cesarean delivery, but were different in the incidence of preeclampsia and preterm labor. Study and control infants were similar in birth weight, GA, indomethacin prophylaxis, early sPDA treatment, mortality, necrotizing enterocolitis, severe intraventricular hemorrhage and stage 3-5 retinopathy of prematurity. Seventeen of 43 study and 16 of 43 control infants who received indomethacin prophylaxis developed sPDA and were combined with early treatment sPDA infants (15 to each group). Two of 32 study and two of 31 control infants underwent surgical ligation whereas the remaining were treated with indomethacin. Sixteen of 30 (53%) and 13 of 29 (45%) were successfully treated and did not require ligation. Study infants were divided according to their mothers' indomethacin total dose (28 infants received p225 mg and 30 infants received >225 mg). Both subgroups were demographically and clinically comparable and their response to indomethacin prophylaxis and treatment were similar. Conclusion:In ELBW infants, exposure to indomethacin tocolysis does not affect the clinical responsiveness of the ductus arteriosus to prophylaxis or that of the sPDA to indomethacin treatment.

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Section: Discussionsupporting

confidence: 91%

The effects of indomethacin tocolysis on the postnatal response of the ductus arteriosus to indomethacin in extremely low birth weight infants

et al. 2006

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“…Our findings are supported by randomized trials 18,19 and by the other two large cohort studies that investigated the efficacy of indomethacin as a tocolytic agent. [24][25][26] Two recent meta-analyses, 4,27 one including 21 observational studies and a second that included 28 studies (17 observational, 11 randomized clinical trials) failed to show a significant association between prenatal indomethacin exposure and either NEC or IIP. Postnatal indomethacin exposure and IIP We found that the odds of IIP were greater among infants who received early (first day) indomethacin treatment for intraventricular hemorrhage prophylaxis, but not among infants who were treated with indomethacin later in their hospital course for a PDA.…”

Section: Prenatal Indomethacin Exposurementioning

confidence: 99%

Prenatal or postnatal indomethacin exposure and neonatal gut injury associated with isolated intestinal perforation and necrotizing enterocolitis

et al. 2010

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Objective: To examine the role of indomethacin in neonatal gut injury.Study Design: Infants born at gestational age X23 weeks and with birth weights 400-1200 g were included in this prospective prevalence study of neonatal gut injury. Infants with isolated intestinal perforation (IIP) confirmed at laparotomy or at autopsy or with necrotizing enterocolitis (NEC) were identified. Data were abstracted bi-weekly.Result: Among 992 study infants, 58 infants exposed solely to prenatal indomethacin did not show an increased rate of neonatal gut injury. Any postnatal indomethacin exposure (n ¼ 611) increased the odds of IIP (OR 4.17, CI, 1.24-14.08, P ¼ 0.02) but decreased the odds of NEC (OR 0.65, CI 0.43-0.97, P ¼ 0.04). There was a negative association between the timing of indomethacin-exposure and the odds of developing IIP (OR 0.30, CI 0.11-0.83, P ¼ 0.02). Compared with NEC, IIP occurred at an earlier age (P<0.05) and was more common (P<0.05) among infants who received early indomethacin (first dose at <12 h of age) to prevent intraventricular hemorrhage than among infants who were treated with late indomethacin for closure of a patent ductus arteriosus (PDA). Unlike the classic hemorrhagic ischemic lesions of NEC in which large areas of tissue were inflamed or necrotic, the IIP lesions were small and discrete.Conclusion: Early (<12 h) postnatal indomethacin exposure was associated with an increased odds of IIP in very low birth weight infants whereas its later use for closure of a PDA appeared to provide protection against NEC. The paradoxical effect of the timing of indomethacin on IIP versus on NEC may be related to the different pathogeneses of the two diseases. Our findings also suggest that PDA may contribute to NEC.

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“…40,42,44 In addition, one case-control study that specifically evaluated congenital heart defects did not find any association with maternal NSAID exposure. 43 Use of NSAIDs late pregnancy has been associated with premature closure of the ductus arteriosus, 27,45,46 neonatal intraventricular haemorrhage, 45,47,48 impaired renal function, 45,49-51 persistent pulmonary hypertension of the newborn, 52,53 necrotising enterocolitis, 45,57 and cere bral palsy (Supplementary Table 2). 54 The plausibility of these reports from a pharmacological point of view warrants their findings to be taken into serious consideration.…”

Section: Paracetamolmentioning

confidence: 98%

Pharmacological treatment of migraine during pregnancy and breastfeeding

et al. 2015

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Migraine affects up to 25% of women of reproductive age. In the majority of these women, migraine improves progressively during pregnancy, but symptoms generally recur shortly after delivery. As suboptimally treated migraine in pregnancy could have negative consequences for both mother and fetus, the primary aim of clinicians should be to provide optimal treatment according to stage of pregnancy, while minimising possible risks related to drug therapy. Nonpharmacological approaches are always first-line treatment, and should also be used to complement any required drug treatment. Paracetamol is the preferred drug for acute treatment throughout pregnancy. If paracetamol is not sufficiently effective, sporadic use of sumatriptan can be considered. NSAIDs such as ibuprofen can also be used under certain circumstances, though their intake in the first and third trimesters is associated with specific risks and contraindications. Preventive treatment should only be considered in the most severe cases. In women contemplating pregnancy, counselling is essential to promote a safe and healthy pregnancy and postpartum period for the mother and child, and should involve a dialogue addressing maternal concerns and expectations about drug treatment. This Review summarizes current evidence of the safety of the most common antimigraine medications during pregnancy and breastfeeding, and provides treatment recommendations for use in clinical practice.

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Outcome of Very Low Birth Weight Infants Exposed to Antenatal Indomethacin for Tocolysis

Cited by 20 publications

References 24 publications

The effects of indomethacin tocolysis on the postnatal response of the ductus arteriosus to indomethacin in extremely low birth weight infants

The effects of indomethacin tocolysis on the postnatal response of the ductus arteriosus to indomethacin in extremely low birth weight infants

Prenatal or postnatal indomethacin exposure and neonatal gut injury associated with isolated intestinal perforation and necrotizing enterocolitis

Pharmacological treatment of migraine during pregnancy and breastfeeding

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