Abstract
Objective
To evaluate the effect of antenatal indomethacin exposure on neurodevelopmental outcomes of premature infants.
Study Design
A retrospective cohort study was performed to compare neurodevelopmental outcomes between premature infants exposed to antenatal indomethacin and infants unexposed to antenatal indomethacin. Inclusion criteria included all 23 – 29 weeks’ gestational age infants delivered between January, 1998 and December, 2002 and who had neurodevelopmental evaluation performed at 16–24 months corrected age. Out born infants and those with major congenital malformations or chromosomal problems were excluded. Continuous and categorical variables were analyzed using t-test and chi-square test, respectively.
Results
87 infants met inclusion criteria. Of 87 infants, 29 infants were exposed to antenatal indomethacin (mean dose 267 mg and median duration 3 days) and 58 infants were unexposed to antenatal indomethacin. There were no significant differences between the two groups in clinical characteristics except for gestational age, mode of delivery and antenatal steroid exposure. There was no significant difference in major neurosensory abnormality (cerebral palsy and/or deafness and/or blindness); however the proportion of infants with sub-normal Bayley-Mental Developmental Index (MDI ≤ 70) and neurodevelopmental impairment (neurosensory abnormality and/or MDI ≤ 70) was significantly less in the group exposed to antenatal indomethacin compared to unexposed group. When controlled for confounders including antenatal steroids, antenatal indomethacin was not associated with MDI ≤ 70 (Odds ratio (OR) 0.44, 95% CI 0.12–1.5) and neurodevelopmental impairment (OR 0.4, 95% CI 0.13–1.2) using logistic regression. Subgroup analysis of 12 infants exposed to antenatal indomethacin within 48 hours of birth was not associated with neurodevelopmental impairment (OR 0.2, 95% CI 0.03–1.02) compared to unexposed group.
Conclusion
Antenatal indomethacin is not associated with abnormal neurodevelopmental outcome in infants ≤ 29 weeks gestational age.
Keywords: Tocolysis, Antenatal Indomethacin, Neurodevelopment, Premature infants
INTRODUCTION
Prematurity continues to be the major cause of neonatal morbidity and mortality. Therefore strategies to prevent preterm labor and subsequent preterm delivery are of major importance. Indomethacin, a prostaglandin inhibitor, is frequently used as a tocolytic agent.1,2 Beside postponing pre-term delivery for varying duration; indomethacin usage may allow sufficient duration to administer antenatal betamethasone. Antenatal betamethasone exposure is known to improve neonatal outcomes.3,4
Indomethacin also crosses the placenta freely and can inhibit the synthesis of prostaglandins in fetal tissues.5,6 Indomethacin is a vasoconstrictor and has been shown to decrease mesenteric, renal and cerebral blood flow in animals that may biologically explain the risk in premature infants for necrotizing enterocolitis (NEC), renal dysfunction and periventricular leukomalacia (PVL), respectively.7–9 A recent meta-analyses of observational studies reported an increased risk of PVL and NEC in premature infants after exposure to antenatal indomethacin.10 Both PVL and NEC are known risk factors for abnormal neurological outcome in premature infants. 11–13
It is yet unclear whether the benefits of delaying preterm delivery and administration of antenatal betamethasone with the use of antenatal indomethacin are outweighed by the potential increase in adverse neonatal outcomes such as PVL and NEC. The question then arises whether exposure to antenatal indomethacin is associated with any beneficial or adverse long-term neurodevelopmental outcome. There is limited data on the long-term neurodevelopmental outcome of premature infants exposed to antenatal indomethacin.14,15 Previous neurodevelopmental studies evaluating the effect of antenatal indomethacin exposure had limited statistical power to detect adverse effects and were performed when antenatal steroids were not routinely used. We conducted a retrospective cohort study to evaluate if exposure to antenatal indomethacin is associated with abnormal neurological outcome in premature infants ≤ 29 weeks at 16–24 months corrected age. The study was approved by the Institutional Research Review Board at the University of Maryland, School of Medicine.
MATERIAL AND METHODS
Study Population
We identified all premature singleton or multiple-gestation infants ≤ 29 weeks gestational age (GA) who were delivered at the University of Maryland Medical Center (UMMC) over a 5-year period from January 1998 to December 2002 using our neonatal database system. GA was determined by best estimate of maternal history, first trimester ultrasound, and physical assessment of the infant by the attending neonatologist. Our inclusion criteria consisted of infants ≤ 29 weeks GA at birth who were delivered between January 1998 and December 2002 at UMMC and had completed neurodevelopmental evaluation at 16–24 months corrected age. Out born infants and infants with major congenital malformation or chromosomal disorders were excluded.
Treatment Variable
Indomethacin is used as a second choice tocolytic agent at UMMC. The standard indomethacin treatment protocol was 100 mg administered intravenously as a loading dose followed by 25 mg rectally or intravenously every 6 hours for 24 hours, and then repeated for another 24 hours at the discretion of the attending obstetrician. The data on antenatal indomethacin exposure including amount, duration and timing of antenatal indomethacin prior to delivery was extracted from pharmacy records on all infants who met study criteria. Infants were classified into two groups: Infants who were exposed to antenatal indomethacin (Group I), and Infants who were unexposed to antenatal indomethacin (Group II). The two groups were compared for neurodevelopmental outcome at 16–24 months corrected age.
Outcome Variables
All premature infants born < 31 weeks GA at UMMC undergo periodic neurodevelopmental evaluation at developmental follow-up clinic. The neurodevelopmental evaluation at 16–24 months corrected age included obtaining developmental histories and performing neurological examination by a neonatologist and confirmation by a developmental pediatrician. The neurological assessment included an evaluation of tone, strength, reflexes, angles, and posture. The major neurological abnormality identified for study purposes was cerebral palsy which may be spastic diplegia, hemiplegia, triplegia or quadriplegia. Cerebral palsy was defined as non-progressive central nervous system disorder characterized by abnormal muscle tone in at least 1 extremity and abnormal control of movement and posture. Revised Bayley Scale of Infant Development (BSID II) was also administered by a trained psychologist at 16–24 months corrected age to evaluate cognitive function using mental developmental index (MDI). Mental developmental index (cognitive function) scores of 100 ± 15 represent the mean ± 1 standard deviation (SD). A score ≤ 70 is 2 SDs below the mean. The neurosensory abnormality included major neurological abnormality and/or unilateral or bilateral blindness and/or unilateral or bilateral deafness. The neurodevelopmental abnormality was defined as neurosensory impairment and/or a mental developmental score (MDI) ≤ 70. The outcome variables were dichotomized depending on the presence or absence of abnormality for the purpose of analyses.
Covariates
Data on demographics, potential confounders, and outcomes were extracted from maternal charts, neonatal charts, and developmental clinic charts by investigators blinded to group assignment. Intraventricular hemorrhage (IVH) grading on head ultrasound findings was based on Papille’s classification and was reported by Pediatric Radiologist. PVL was defined based on head ultrasound findings and reported by Pediatric Radiologist. Head ultrasounds were performed during first week, at the end of second week, at 1 month and at discharge. Bronchopulmonary dysplasia (BPD) was defined based on oxygen requirement at 36 weeks post-menstrual age. NEC was defined based on X-ray findings of pneumatosis and/or free air in peritoneum that were reported by Pediatric Radiologist.
Statistical analyses
Statistical analysis was performed using Stata 8 (Stata Corporation, College Station, TX). Student t-test and Chi-square analysis were used to analyze continuous and categorical variables respectively. An alpha of 0.05 was considered statistically significant. Odds ratio and 95% confidence interval were computed for outcomes. Stratified analyses with Breslow Dey homogeneity tests and Mantel-Haenszel tests were used to evaluate for possible effect modifiers and confounders. Bivariate analyses were performed to evaluate the association between clinical variables (covariates) and antenatal indomethacin (main exposure). Similarly, bivariate analyses were performed to evaluate the association between covariates and neurodevelopmental outcomes in subjects unexposed to antenatal indomethacin. Covariates with significant association (p < 0.2) to antenatal indomethacin exposure or neurodevelopmental outcome were considered as possible confounders and included in model building for regression analyses. Final model building was performed using backward selection method. Log likelihood ratio test was performed to evaluate the inclusion of potential confounders (based on bivariate analyses) in the regression model. Covariates that did not make a statistically significant contribution to the model as evaluated by the log likelihood ratio test were removed from the model. The final model was evaluated for a fitness using Hosmer Lemeshow test. A logistic regression analysis was performed using final model to control for potential confounding factors. Since antenatal steroid may be considered as an intermediate in the causal pathway between antenatal indomethacin and neurodevelopmental outcome, regression analyses were performed with and without including antenatal steroid as a covariate in the model.
Sample size calculation
An approximate sample size was determined for the number of neonates to be studied based on earlier findings of neurodevelopmental outcome in similar population.16 Based on earlier findings of 35% incidence of neurodevelopmental impairment in similar population, 37 subjects in each group would allow detection of 20% difference in the proportion of infants with neurodevelopmental impairment for ≤ 29 weeks’ gestational age infants with an α level of 0.05 and a power of 0.80.
RESULTS
From the neonatal database, we identified a total of 2,225 infants admitted to Neonatal Intensive Care Unit (NICU) between January 1998 and December 2002, of which 1529 were inborn infants. Of 1529 inborn infants, 255 infants were born at ≤ 29 weeks GA. Of these 255 infants, 7 infants with chromosomal disorders or major congenital malformations were excluded. Forty four infants died in NICU (14 from sepsis, 6 from pulmonary hemorrhage, 12 from respiratory failure, 6 from NEC, 3 from renal failure, 3 from grade IV IVH.) Of the remaining 204 infants ≤ 29 weeks GA, 87 had neurodevelopmental evaluation performed at 16 to 24 months corrected age. Of these 87 infants who had neurodevelopmental evaluation performed at 16–24 months corrected age, 29 infants were exposed to antenatal indomethacin and 58 infants were not exposed to antenatal indomethacin. Indomethacin treated mothers received a mean total dose of 267 mg (range 50–950 mg). The median duration of treatment was 3 days (range 1–31 days). Mothers of infants unexposed to antenatal indomethacin either received no tocolytic therapy or received magnesium sulfate for tocolysis.
The clinical characteristics of 44 infants who died while in the NICU were no different than the 87 infants who completed neurodevelopmental evaluation at 16–24 months corrected age. Majority (95%) of these infants died within the first 2 weeks after birth. There was no significant difference in mortality between infants who were exposed to antenatal indomethacin and infants who were not exposed to antenatal indomethacin. There was no significant difference in clinical characteristics of infants except for gestational age at birth between infants who completed 16–24 months neurodevelopmental evaluation (n = 87) and infants who were lost to follow-up at 16–24 months (n = 117). The mean gestational age at birth (26.2 weeks) of infants who completed neurodevelopmental evaluation was significantly less compared to mean gestational age at birth (26.8 weeks) of infants who were lost to follow-up at 16–24 months corrected age.
The clinical characteristic of infants who completed neurodevelopmental evaluation as a function of antenatal indomethacin exposure is shown in Table I. There was no significant difference between the two groups in clinical characteristics except for gestational age, mode of delivery and antenatal steroid exposure. Infants in antenatal indomethacin exposed group were more mature compared to unexposed group. Similarly, proportion of infants exposed to antenatal betamethasone was higher in antenatal indomethacin group compared to group of infants unexposed to antenatal indomethacin. Neonatal outcomes as a function of antenatal indomethacin exposure are summarized in Table II. There was no statistically significant difference between the two groups in the incidence of sepsis, respiratory distress syndrome (RDS), patent ductus arteriosus (PDA), Grade III–IV (severe) IVH, PVL, BPD and NEC. There was also no significant difference between the two groups in the proportion of infants who received postnatal indomethacin and postnatal dexamethasone.
Table I.
Demographic characteristics as a function of antenatal indomethacin exposure (n = 248).
| Antenatal Indomethacin Exposed (N = 85) |
Antenatal Indomethacin Unexposed (N = 163) |
P** | |
|---|---|---|---|
| Gestational age (wks)* | 26.1 ± 1.8 | 26.4 ± 1.8 | 0.3 |
| Birth weight (grams)* | 889 ± 267 | 915 ± 239 | 0.5 |
| Race (% of African American) | 69 | 67 | 0.7 |
| Gender (Male/Female) | 47/38 | 76/87 | 0.2 |
| Mode of delivery (% C-section) | 28 | 49 | 0.04 |
| Apgar < 3 at 5 minutes (%) | 5 | 8 | 0.2 |
| Antenatal steroid exposure (%) | 80 | 55 | 0.00 |
| Other tocolytic agent (%) | 80 | 60 | 0.03 |
| Maternal illicit drug use (%) | 9 | 23 | 0.05 |
| Clinical chorioamnionitis (%) | 20 | 26 | 0.3 |
| Maternal education ≥ college (%) | 67 | 65 | 0.8 |
| Mortality (%) | 18 | 18 | 0.9 |
| Lost to follow-up (%) | 59 | 57 | 0.8 |
Mean ± SD
using t-test for continuous and Chi-square test for categorical variables
Table II.
Clinical characteristics of subjects (n =204) as a function of neurodevelopmental evaluation
| Infants who were lost to follow-up (N = 117) |
Infants who had neurodevelopmental evaluation (N = 87) |
P** | |
|---|---|---|---|
| Gestational age at birth (weeks)* | 26.8 + 1.7 | 26.2 + 1.6 | 0.01 |
| Culture proven sepsis (%) | 58 | 53 | 0.5 |
| RDS (%) | 77 | 76 | 0.8 |
| PDA (%) | 71 | 68 | 0.7 |
| Postnatal indomethacin (%) | 65 | 64 | 0.8 |
| IVH III/IV (%) | 10 | 16 | 0.1 |
| PVL (%) | 7 | 13 | 0.3 |
| BPD @ 36 weeks (%) | 41 | 50 | 0.1 |
| Postnatal dexamethasone (%) | 22 | 32 | 0.09 |
| NEC (perforation or pneumatosis) (%) | 7 | 8 | 0.1 |
| Hospital stay* | 74 ± 27 | 79 ± 26 | 0.3 |
Mean ± SD
using t-test for continuous and Chi-square or Fisher exact test for categorical variables
The unadjusted neurodevelopmental outcome as a function of antenatal indomethacin exposure is shown in Table III. There was no significant difference in neurosensory abnormality between the two groups. There were significant differences (p < 0.05) in the proportion of infants with MDI ≤ 70 and neurodevelopmental impairment (neurosensory abnormality and/or MDI ≤ 70) between the two groups with fewer infants exposed to antenatal indomethacin having MDI ≤ 70 and neurodevelopmental impairment compared to unexposed group (Table III). To adjust for possible confounders, we performed logistic regression analyses for these two outcomes that were associated with antenatal indomethacin exposure.
Table III.
Demographic characteristics as a function of antenatal indomethacin- exposure for subjects who had neurodevelopmental evaluation. (n = 87)
| Antenatal Indomethacin Exposed (N = 29) |
Antenatal Indomethacin Unexposed (N = 58) |
P** | |
|---|---|---|---|
| Gestational age (wks)* | 25.7 ± 1.4 | 26.4 ± 1.6 | 0.02 |
| Birth weight (grams)* | 840 ± 251 | 881 ± 237 | 0.46 |
| Race (% of African American) | 76 | 72 | 0.36 |
| Gender (Male/female) | 14/15 | 24/34 | 0.54 |
| Mode of delivery (% C-section) | 22 | 50 | 0.02 |
| Infants with Apgar < 3 at 5 minutes (%) | 3 | 5 | 0.22 |
| Infants exposed to antenatal steroid (%) | 96 | 75 | 0.02 |
| Other tocolytic agent (%) | 88 | 71 | 0.07 |
| Maternal illicit drug use (%) | 9 | 25 | 0.1 |
| Clinical chorioamnionitis (%) | 14 | 21 | 0.41 |
| Histological chorioamnionitis (%) | 90 | 68 | 0.07 |
| Maternal education ≥ college (%) | 77 | 61 | 0.17 |
Mean ± SD
using t-test for continuous and Chi-square test for categorical variables
The covariates gestational age at birth, BPD and antenatal steroids were identified as confounders for the outcome neurodevelopmental impairment using log likelihood ratio test and were included in the final logistic regression model. The Hosmer Lemeshow test suggested that there was no difference in the expected frequencies and observed frequencies and that the model was a good fit (p = 0.68). Similarly, using backward selection method and log likelihood ratio test, gestational age at birth, BPD, PDA, IVH and antenatal steroids were identified as confounders and included in the final model for the outcome MDI ≤ 70. The Hosmer Lemeshow test suggested that the model for the outcome MDI was a good fit (p = 0.81).
Table IV demonstrates the adjusted MDI ≤ 70 and neurodevelopmental impairment as a function of antenatal indomethacin exposure. On controlling for confounding variables including antenatal steroid exposure, antenatal indomethacin was not associated with MDI ≤ 70 (Adj. OR 0.44, 95% CI 0.12–1.5) or neurodevelopmental impairment (Adj. OR 0.4, 95% CI 0.13–1.2). On controlling for confounding variables other than antenatal steroid exposure, antenatal indomethacin exposure was significantly associated with neurological outcomes. Antenatal indomethacin exposure is associated with 71% decreased risk of MDI ≤ 70 and 68% decreased risk of neurodevelopmental impairment compared to infants unexposed to antenatal indomethacin controlling for respective covariates listed in Table IV. On sub-group analysis of 12 infants exposed to antenatal indomethacin within 48 hrs of birth, antenatal indomethacin was not associated with neurodevelopmental impairment (Adj. OR 0.2, 95% CI 0.03–1.02).
Table VI.
Adjusted neurodevelopmental outcome as a function of antenatal indomethacin exposure with and without controlling for antenatal steroids exposure
| Outcome Covariates |
When controlled for antenatal steroid exposure* Adjusted Odds ratio* (95% CI) |
When not controlled for antenatal steroid exposure** Adjusted Odds ratio* (95% CI) |
|---|---|---|
| MDI ≤ 70 | ||
| Antenatal indomethacin | 0.44 (0.12 – 1.5) | 0.29 (0.03 – 0.95) |
| Antenatal steroid | 0.09 (0.03 – 1.13) | |
| PDA | 3.3 (0.85 – 13) | 4.1 (1.1 – 15) |
| BPD | 5.6 (1.5 – 19) | 6.4 (1.9 – 22) |
| IVH III/IV | 19 (1.7 – 213) | 17 (1.5 – 193) |
| Gestational age at birth (weeks) | 0.52 (0.13 –1.97) | 0.40 (0.11 –1.48) |
| Neurodevelopmental impairment | ||
| Antenatal indomethacin | 0.40 (0.13 – 1.2) | 0.32 (0.11 – 0.92) |
| Antenatal steroid | 0.33 (0.07 – 1.47) | |
| BPD | 7.4 (2.4 – 23.3) | 8.0 (2.6 – 24.6) |
| Gestational age at birth (weeks) | 0.74 (0.24 – 2.3) | 0.68 (0.22 – 2.09) |
logistic regression analyses with antenatal steroid exposure in the model
logistic regression analyses without antenatal steroid exposure in the model
COMMENT
Indomethacin has been shown to postpone preterm delivery 1,2 for sufficient duration to allow for the optimal use of antenatal betamethasone, and therefore the reduction in the incidence of RDS, NEC, PVL and IVH.3,4 However there is a concern about the safety of antenatal indomethacin usage because indomethacin crosses the human placenta throughout the pregnancy and has the potential to cause adverse fetal and neonatal effects.5, 7–9 A recent meta-analyses on observational studies concluded that antenatal indomethacin may be associated with an increased risk of PVL and NEC in premature infants.10 Both PVL and NEC are independently associated with abnormal neurodevelopmental outcome.11–13 In order to consider indomethacin as a tocolysis, the adverse neonatal effects of antenatal indomethacin should be balanced by significantly more favorable developmental outcome of the survivors resulting from the optimal use of antenatal betamethasone and postponement of preterm delivery. Our findings suggest that antenatal indomethacin used as tocolysis is not associated with adverse neurodevelopmental outcome at 16–24 months corrected age in infants ≤ 29 weeks GA. In fact, our findings suggest that antenatal indomethacin may be associated with an improved neurological outcome if not adjusted for antenatal steroid exposure.
Antenatal indomethacin is often used as a second tocolysis to postpone delivery for sufficient duration to administer a course of betamethasone known to have beneficial effects on premature infant. It appears that both preterm delivery and antenatal steroid exposure fall as intermediates in a causal pathway between antenatal indomethacin and neurological outcomes. On statistical grounds one may therefore argue that antenatal steroid exposure and postponement of preterm delivery should not be considered as confounders for the effect of antenatal indomethacin on neurological outcomes. Secondly, adjusting for antenatal steroid exposure in studies using antenatal indomethacin tocolysis could lead to an underestimate of benefit associated with postponing preterm delivery. If antenatal steroid exposure is not treated as a confounder, then our findings suggest that antenatal indomethacin may be associated with improved long-term neurological outcome. It is difficult to accurately measure postponement of preterm delivery without knowing the gestation at onset of preterm labor. The information on gestation at the onset of preterm labor was not available in most cases and therefore we could not measure postponement of preterm delivery.
Our findings of a possible improved long-term neurological outcome following antenatal indomethacin exposure are different from the two published studies. Salokorpi et al.14 in a follow-up study of a randomized trial comparing antenatal indomethacin with nyldrin reported that antenatal indomethacin was non-significantly associated with abnormal neurological outcome in premature infants when evaluated at 18 months corrected age. However, the study was performed when antenatal steroids were not routinely used. None of the subjects in Salokorpi’s study were exposed to antenatal steroids. The beneficial effects of antenatal steroids may outweigh the risk associated with the use of antenatal indomethacin as suggested by our findings. Similarly Al-alaiyan15 in a small retrospective cohort study of 23 infants concluded that there is no effect of antenatal indomethacin on neurodevelopmental outcome at 12 months of age. However, the study failed to account for possible confounders. Secondly, a possibility of type II error remains with extremely small sample in the study reported by Al-alaiyan et al. The strengths of our study include evaluation of the effect of antenatal steroids and adjustment for possible confounders. Our findings are in agreement to the findings reported by Macones and Robinson17 using decision analysis model. Their decision analysis model supports the use of indomethacin for tocolysis to decrease adverse neonatal outcomes by allowing the administration of a complete course of betamethasone.
The major limitation of our study is its retrospective nature and associated selection and information bias. The possibility of selection bias can not be excluded as there were no set criteria for the use of indomethacin as a tocolytic agent. Also we do not know long-term neurological outcomes of the infants who were lost to follow-up at 16–24 months developmental evaluation. However infants who were lost to follow-up at 16–24 months had similar clinical characteristics to infants who had developmental evaluations performed at 16–24 months corrected age. Another limitation of our observational study is that the results mainly reflect the effect of antenatal indomethacin when used for recalcitrant labor. A potential cause for recalcitrant labor could be overt or silent chorioamnionitis 18 which has recently been associated with PVL, NEC, BPD and abnormal neurological outcomes.19,20 We observed a non-significant increased risk of silent chorioamnionitis in the group exposed to antenatal indomethacin compared to unexposed group. We also observed a non-significant increased risk of PVL in infants exposed to antenatal indomethacin compared to infants unexposed to antenatal indomethacin. Whether the adverse neonatal effects such as PVL are secondary to the recent exposure to antenatal indomethacin or to underlying silent chorioamnionitis, a marker of recalcitrant labor, remains to be answered. If the adverse neonatal effects such as PVL and NEC are secondary to underlying silent chorioamnionitis that is usually associated with recalcitrant labor, then the use of antenatal indomethacin as a first choice tocolytic agent may be associated with a better long- term neurological outcome compared to the outcome associated with the use of indomethacin for recalcitrant labor.
In summary, our findings suggest that antenatal indomethacin usage for recalcitrant labor is not associated, or possibly is inversely associated, with abnormal neurological outcome at 16–24 months corrected age. Because of the limitations cited above, an appropriately sized prospective, randomized trial of indomethacin as a tocolytic agent with adequate retention of enrolled premature infants for a complete neurodevelopmental evaluation at 2years and beyond is warranted to determine the long-term safety of antenatal indomethacin therapy.
Table V.
Neurodevelopmental outcome as a function of antenatal indomethacin exposure (unadjusted).
| Antenatal Indomethacin Exposed (N = 29) |
Antenatal Indomethacin Unexposed (N = 58) |
p* | |
|---|---|---|---|
| Cerebral palsy (n) | 7 (24%) | 16 (28% | 0.7 |
| Unilateral or bilateral deafness (n) | 4 (14%) | 5 (8%) | 0.4 |
| Unilateral or bilateral blindness (n) | 1 (3%) | 2 (3%) | 0.9 |
| MDI ≤ 70 (n) | 10 (35%) | 36 (63%) | 0.01 |
| Neurosensory abnormality (n) | 7 (24%) | 18 (31%) | 0.5 |
| Neurodevelopmental impairment (n) | 13 (45%) | 39 (67%) | 0.04 |
using Chi-square test or Fisher exact test
ACKNOWLEDGMENT
We are grateful to Edwin van Wijngaarden, Ph.D for review of the paper. The study was performed as part of a clinical investigational training towards Masters in Clinical Research and was funded by K-23 NIH grant DC 06229.
Abbreviations
- IRB
Institutional Review Board
- AI
Antenatal Indomethacin
- IVH
Intraventricular Hemorrhage
- PVL
Periventricular Leukomalacia
- NEC
Necrotizing Enterocolitis
- MDI
Mental developmental Index
- PDI
Psychomotor Developmental Index
- BSID
Bayley scale of Infant Development
- BPD
Bronchopulmonary dysplasia
- RDS
Respiratory Distress Syndrome
- ROP
Retinopathy of Prematurity
- SD
Standard Deviation
- OR
Odds Ratio
- CI
Confidence Interval
Footnotes
Presented at the Pediatric Academic Society Meeting held in San Francisco on May 1, 2006
CONDENSATION Antenatal indomethacin is not associated with adverse neurodevelopmental outcome in premature infants ≤ 29 weeks’ gestational age infants
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