Table 1.

Characteristics of the included studies^a

Author, year	Study design	Country	Study Interval	Cases/subjects	Exposure	Adjusted risk estimate (95% CI)	Quality	Adjustment variables
Infant exposure
Eberly,2015 [21]	R-COH	USA	2001–2012	2466/1074236	Erythromycin: 0–14 days 15–42 days 43–90 days 0–90 days Azithromycin: 0–14 days 15–42 days 0–90 days	13.3 (6.8–25.9) 4.1 (1.69–9.91) 1.19 (0.38–3.71) 3.94 (2.44–6.36) 8.26 (2.62–26) 2.98 (1.24–7.2) 0.71 (0.36–1.43)	9	firstborn status, gender, and the year of the birth
Ericson,2015 [22]	R-COH	USA	1997–2012	86/20196	Metoclopramide vs Erythromycin (0–120 days)	0.52 (0.26–1.02)	9	Gestational age at birth, small-for-gestational-age status, severity of illness, and age at first medication exposure
Lund,2014 [26]	R-COH	Denmark	1996–2011	849/998529	Erythromycin: 0–13 days 14–120 days	Rate Ratio: 29.8 (16.4–54.1) 3.24 (1.2–8.74)	9	birth order, gender, calendar period, current age of the infant, gestational age at birth, small for gestational age status, caesarean section, major congenital malformations, and maternal smoking during pregnancy
Cooper, 2002 [19]	R-COH	USA	1985–1997	804/314029	Erythromycin: 3–13 days 14–27 days 28–90 days Any use	incidence rate ratio: 7.88 (1.97–31.57) 0.92 (0.13–6.57) 1.95 (0.87–4.38) 2.05 (1.06–3.97)	9	Child’s age, sex, and race
Mahon, 2001 [27]	R-COH	USA	1993–1999	43/14876	Erythromycin: ≤1 week ≤2 week ≤3 months	10.62 (4.2–26.7) 10.51 (4.5–24.7) 4.98 (2.1–11.7)	7	NR
Honein,1999 [23]	R-COH	USA	Jan - Feb, 1999	7/282	Erythromycin	∞ (1·7–∞)	6	Not adjusted
Ludvigsson, 2016 [4]	R-COH	Sweden	2005–2010	450/582494	Macrolides (0–120 days)	NR	6	NR
Maternal use during pregnancy
Mahon, 2001 [27]	R-COH	USA	1993–1999	43/14876	Erythromycin: Any time during pregnancy	1.19 (0.6–2.3)	7	NR
Cooper, 2002 [20]	R-COH	USA	1985–1997	679/260799	Erythromycin: Any time during pregnancy ≥ 32 weeks Other macrolides: Any time during pregnancy ≥ 32 weeks	1.15 (0.84–1.56) 1.17 (0.84–1.64) 2.77 (1.22–6.30) 2.45 (0.78–7.68)	9	sex, race, first-born status, year of birth, and infant’s postnatal prescriptions for erythromycin
Källén, 2005 [24]	R-COH	Sweden	1995–2002	464/677028	Erythromycin: Any time during pregnancy 1st trimester	2.51 (0.92–5.46) 3.03 (1.08–8.50)	7	NR
Rookkapan, 2008 [25]	R-COH	Denmark	1991–2005	NR/176905	Erythromycin: Any time during pregnancy	1.05 (0.43–2.55)	7	NR
Dinur, 2013 [18]	R-COH	Israel	1999–2009	50/102831	Macrolides: 3rd trimester	NR	7	Not adjusted
Lund,2014 [26]	R-COH	Denmark	1996–2011	877/999378	Macrolides: 0–27 weeks ≥28 weeks	1.02 (0.65–1.59) 1.77 (0.95–3.31)	9	birth order, sex, calendar period, and current age of the infant
Louik, 2002 [29]	C-C	USA	1976–1998	1044/1704	Erythromycin: 1–24 weeks 25–40 weeks 33–40 weeks	1.0 (0.6–1.6) 0.6 (0.3–1.1) 0.7 (0.3–1.8)	8	maternal age, geographical region, study period, parity, sex of infants, gestational age
Lin,2013 [28]	C-C	USA/Canada	1994 to 2008	735/6952	Erythromycin: 1st trimester 2nd trimester 3rd trimester Macrolides: 1st trimester 2nd trimester 3rd trimester	0.9 (0.3–3.0) 1.5 (0.4–4.8) 1.5 (0.5–5.1) 1.3 (0.6–2.8) 1.3 (0.5–3.0) 1.3 (0.6–2.9)	8	residence and year, maternal age, race, education, pre-pregnancy BMI, family history of congenital malformations, diabetes mellitus, first trimester cigarette smoking, peri-conceptional folic acid supplement, multiple pregnancy, infections, sexually transmitted disease, febrile events
Maternal use after birth
Lund,2014 [26]	R-COH	Denmark	1996–2011	849/999378	Macrolides: 0–13 days 14–120 days	Rate Ratio: 3.49 (1.92–6.34) 0.7 (0.26–1.9)	9	birth order, sex, calendar period, and current age of the infant, age at birth, small for gestational age, caesarean section, major congenital malformations, and maternal smoking during pregnancy
SØRENSEN, 2003 [2]	R-COH	Denmark	1991–2000	78/35856	Macrolides: (0–42 days)	2.8 (0.7–11.5)	9	maternal age, birth order and smoking status

^a Abbreviations: R-COH: Retrospective cohort studies; C-C: case-control studies; CI: Confidence Interval; NR: Not Reported