Increase Otitis Media Risk in Children With Antibiotic Use During Pregnancy

Intake of antibiotics during pregnancy increases the risk of developing otitis media and requiring treatment with ventilation tubes in children early in life, according to a study published in The Journal of Pediatrics.

Tina M. Pedersen, MD, from the University of Copenhagen in Denmark, and colleagues conducted an observational, single-center study using data from 700 children in the Copenhagen Prospective Studies on Asthma in Childhood 2010, an ongoing unselected birth cohort study. Mothers were recruited from 2008 to 2010 at pregnancy week 24; mothers with chronic cardiac, endocrine, renal, or pulmonary disease other than asthma were excluded from the study. Children were included at 1 week of age and followed prospectively by pediatricians with scheduled visits at 1 week and 1, 3, 6, 12, 18, 24, 30, and 36 months of age.

Information on maternal antibiotic use was collected prospectively using The Danish National Prescription Registry, which contains information on all procedures, contacts, and medical prescriptions within the healthcare system linked by a unique personal identification number. Intake of antibiotics was further validated by interviews with the participants.

Episodes of otitis media (n = 514) were registered using a structured daily symptom diary from birth to 3 years of age, and episodes with >90% valid diary information were included in the analyses. Information on treatment with ventilation tubes (n = 699) was extracted from 2 national registries.

There was 37% (n = 256) maternal antibiotic use during pregnancy, and this was associated with an increased risk of otitis media in children (adjusted hazard ratio [HR] 1.30; 95% CI, 1.04-1.63, P =.02). Compared with mothers who were not treated with antibiotics, the incidence of otitis media was statistically significantly increased in mothers treated with respiratory tract infection (RTI) antibiotics, specifically in the third trimester, and mothers treated with antibiotics in the second trimester (Table 1). There was “a dose-response relationship between the number of antibiotic treatments during pregnancy and the risk of otitis media (per-level aHR 1.20; 95% CI, 1.04-1.40, P =.02),” the researchers observed. No effect of urinary tract infection (UTI) antibiotics on the risk of otitis media was observed.

Table 1. Maternal Antibiotics Use and Risk of Otitis Media

	Adjusted HR (95% CI)	P Value
RTI antibiotics	1.45 (1.11-1.89)	.006
Third-trimester RTI antibiotics	1.84 (1.24-2.74)	.003
Second-trimester antibiotics	1.40 (1.06-1.85)	.02

RTI = respiratory tract infection

Compared with mothers who were not treated with antibiotics, treatment in children with ventilation tubes was statistically significantly increased in mothers treated with UTI antibiotics and mothers treated with antibiotics in the third trimester (Table 2). No association between ventilation tube placement and RTI antibiotics was observed.

Table 2. Maternal Antibiotics Use and Risk of Treatment With Ventilation Tubes

	Adjusted HR (95% CI)	P Value
UTI antibiotics	1.56 (1.10-2.19)	.01
Third-trimester antibiotics	1.60 (1.08-2.36)	.02

UTI = urinary tract infection

The risk of otitis media was primarily associated with the use of RTI antibiotics and not UTI antibiotics. Conversely, the risk of treatment with ventilation tubes was associated with UTI antibiotics and not RTI antibiotics. Overall, this effect was isolated to the third trimester of pregnancy.

“Antibiotics can alter the composition of the microbiome and a disturbance in the maternal bacterial ecology would presumably have the greatest impact on vertical transmission if occurring shortly before birth,” noted Dr Pedersen and colleagues. In fact, when stratifying the analysis into different modes of delivery, children born by vaginal delivery were affected more by antibiotic intake compared with children born by cesarean section (Table 3).

Table 3. Antibiotic Intake Effect Compared With Cesarean vs Vaginal Delivery

	Adjusted HR (95% CI)
	Cesarean Delivery	Vaginal Delivery
Otitis Media	1.23 (0.95-1.59) P =.11	1.70 (1.01-2.89) P =.05
Ventilation Tubes	0.96 (0.67-1.38) P =.81	1.97 (0.97-3.98) P =.06

 

“This finding could indicate that microbial alterations caused by the antibiotics in the mother lead to increased disease susceptibility by vertical transmission of an unfavorable composition during birth,” the researchers concluded.

Reference

Pedersen TM, Stokholm J, Thorsen J, Mora-Jensen AC, Bisgaard H. Antibiotics in pregnancy increase children’s risk of otitis media and ventilation tubes [published online January 17, 2016]. J Pediatr. doi: 10.1016/j.jpeds.2016.12.046