The paper by Tyler et al provides novel data on the important issue of brain damage and maternal medication, on which currently there is little published literature.

The authors report a positive association between maternal aspirin use during pregnancy and quadriparesis and between maternal nonsteroidal antiinflammatory drug (NSAID) use during pregnancy and quadriparesis and diparesis in infants who are delivered very preterm. Their discussion highlights the possibilities for confounding by indication and the need for replication in larger cohorts.

Using an already recruited cerebral palsy cohort, we were able to replicate part of these analyses as 145 quadriplegic, 149 diplegic, and 191 hemiplegic infants. This is a cohort with 3-11 times the number of each cerebral palsy subtype compared with that reported by Tyler et al but recruited from deliveries at all gestational ages. Our cohort had insufficient power to replicate independently the associations that were reported by Tyler et al in very preterm infants (68 infants with cerebral palsy were born at <28 weeks’ gestation); however, for all gestational ages, no association was apparent with aspirin and NSAID use and cerebral palsy outcomes.

In contrast, we report negative associations of maternal antibiotic use with diplegia and hemiplegia ( Table ) which was unexpected because perinatal infection is a risk factor for cerebral palsy.

TABLE

Maternal medications and association with cerebral palsy subtypes

Maternal medication	Control subjects (n = 1154) n (%)	Quadriplegia (n = 145) n (%)	Odds ratio a (95% CI)	P value	Diplegia (n = 149) n (%)	Odds ratio a (95% CI)	P value	Hemiplegia (n = 191) n (%)	Odds ratio a (95% CI)	P value	All cases with cerebral palsy (n = 587) n (%)	Odds ratio a (95% CI)	P value
Antibiotics	58 (5)	7 (4.8)	0.3 (0.09–1.01)	.052	11 (7.4)	0.17 (0.06–0.52)	.002	15 (7.9)	0.17 (0.07–0.41)	< .001	40 (6.8)	4.08 (2.08–8.0)	< .001
Aspirin	4 (0.3)	0	—		1 (0.7)	—		1 (0.5)	—		5 (0.9)	0.94 (0.11–8.18)	.95
Nonsteroidal antiinflammatory drugs	9 (0.8)	1 (0.7)	1.57 (0.11–22.4)	.74	1 (0.7)	1.6 (0.11–22.97)	.73	3 (1.6)	0.41 (0.1–1.69)	.217	9 (1.5)	1.41 (0.4–4.91)	.59
Paracetamol	265 (23)	25 (17.2)	1.26 (0.68–2.33)	.465	29 (19.5)	0.7 (0.4–1.23)	.215	51 (27)	0.66 (0.44–1.01)	.056	125 (22)	1.25 (0.91–1.72)	.17

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