Use of Antibiotic Treatment in Pregnancy and the Risk of Several Neonatal Outcomes: A Population-Based Study
Abstract
:1. Background
2. Methods
2.1. Setting
2.2. Study Cohort
2.3. Exposure to Antibiotics
2.4. Outcomes
2.5. Maternal Covariates
2.6. Statistical Analyses
2.7. Sensitivity and Subgroup Analyses
3. Results
3.1. Study Cohort and Outcomes
3.2. Use of Antibiotics and Neonatal Outcomes
4. Discussion
- Limited evidence is available on the safety and efficacy of antimicrobials during pregnancy.
- The concerns about the implications of antibiotics use during pregnancy on adverse neonatal outcomes involve the need for observational studies to assess the potential association between the use of antibiotics during pregnancy and several neonatal outcomes.
- Our results suggested an increased risk of several neonatal outcomes in women who were exposed to antibiotics during pregnancy.
- How the observed effects are due to the infections or the direct action of the considered antimicrobial drugs remains an important open question.
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Maternal Characteristics | Early Users (a) | No Users (a) | SD | Late Users (b) | No Users (b) | SD |
---|---|---|---|---|---|---|
(N = 132,024) | (N = 564,292) | (N = 76,921) | (N = 696,316) | |||
Socio-demographics | ||||||
Age, mean (SD) (c) | 32.7 (5.3) | 32.3 (5.1) | 0.08 | 32.2 (5.4) | 32.4 (5.1) | −0.04 |
No Italian nationality (c,d) | 29,180 (23.03%) | 121,975 (22.48%) | 0.01 | 18,725 (25.39%) | 151,155 (22.58%) | 0.07 |
Unmarried status (c,d) | 40,353 (31.85%) | 167,681 (30.9%) | 0.02 | 22,615 (30.66%) | 208,034 (31.08%) | −0.01 |
Education lower than high school (c,d) | 35,523 (28.03%) | 133,125 (24.53%) | 0.08 | 22,842 (30.97%) | 168,648 (25.2%) | 0.13 |
Unemployed (c,d) | 35,892 (28.32%) | 142,578 (26.27%) | 0.05 | 23,772 (32.23%) | 178,470 (26.66%) | 0.12 |
Previous miscarriages (c) | 34,601 (26.21%) | 134,620 (28.86%) | −0.06 | 20,505 (26.66%) | 169,221 (24.3%) | 0.05 |
Primigravida (c,d) | 37,068 (29.25%) | 17,4241 (32.11%) | −0.06 | 20,601 (27.93%) | 211,309 (31.57%) | −0.08 |
Comorbidities (e) | ||||||
Substance dependence | 52 (0.04%) | 155 (0.03%) | 0.01 | 37 (0.05%) | 207 (0.03%) | 0.01 |
Infection | 4383 (3.32%) | 11,955 (2.12%) | 0.07 | 4674 (6.08%) | 27,942 (4.01%) | 0.09 |
Hypertension | 232 (0.18%) | 842 (0.15%) | 0.01 | 118 (0.15%) | 1074 (0.15%) | 0 |
Preeclampsia | 105 (0.08%) | 393 (0.07%) | 0 | 61 (0.08%) | 498 (0.07%) | 0 |
Diabetes | 328 (0.25%) | 1325 (0.22%) | 0.01 | 211 (0.27%) | 1563 (0.22%) | 0.01 |
Obesity and overweight | 149 (0.11%) | 372 (0.07%) | 0.01 | 123 (0.16%) | 521 (0.07%) | 0.03 |
Dyslipidaemia | 12 (0.01%) | 37 (0.01%) | 0 | 10 (0.01%) | 49 (0.01%) | 0 |
Pain | 609 (0.46%) | 2135 (0.38%) | 0.01 | 399 (0.52%) | 2744 (0.39%) | 0.02 |
C-section (f) | 39,092 (29.61%) | 150,491 (26.67%) | 0.07 | 21,449 (27.88%) | 189,583 (27.23%) | 0.01 |
Concomitant medications (e) | ||||||
NSAIDs | 8680 (6.57%) | 23,117 (4.1%) | 0.11 | 5171 (6.72%) | 31,797 (4.57%) | 0.09 |
Drugs for acid-related disorders | 14,264 (10.8%) | 38,733 (6.86%) | 0.14 | 8274 (10.73%) | 52,997 (7.61%) | 0.11 |
Healthcare utilization (e) | ||||||
Hospital admissions | 26,706 (20.23%) | 106,000 (18.78%) | 0.04 | 1586 (20.62%) | 132,706 (19.06%) | 0.04 |
No. of distinct prescription drugs, excluding antibiotics | ||||||
=1 | 40,903 (30.98%) | 16,8528 (29.87%) | 0.02 | 23,531 (30.59%) | 209,431 (30.08%) | 0.01 |
≥2 | 43,965 (33.3%) | 12,6129 (22.35%) | 0.25 | 24,831 (32.28%) | 170,094 (24.43%) | 0.17 |
Early Users | Late Users | |||||
---|---|---|---|---|---|---|
Entire Cohort | Women Who Experienced Neonatal Outcome | OR (95% CI) | Entire Cohort | Women Who Experienced Neonatal Outcome | HR (95% CI) | |
Preterm birth | ||||||
Cephalosporins | 7816 (1.1%) | 429 (5.5%) | 1.23 (1.12–1.36) | 4113 (0.5%) | 204 (4.9%) | 1.40 (1.22 to 1.61) |
Penicillins | 84,211 (12.1%) | 3970 (4.7%) | 1.12 (1.08–1.16) | 45,285 (5.9%) | 1679 (3.7%) | 1.12 (1.07 to 1.18) |
Macrolides | 24,763 (3.6%) | 1303 (5.3%) | 1.22 (1.15–1.30) | 8402 (1.1%) | 472 (5.6%) | 1.58 (1.44 to 1.73) |
Fluoroquinolones | 6352 (0.9%) | 310 (4.9%) | 1.08 (0.96–1.21) | 1340 (0.2%) | 57 (4.2%) | 1.21 (0.93 to 1.57) |
Other | 24,715 (3.6%) | 1243 (5.0%) | 1.18 (1.11–1.25) | 12,158 (1.6%) | 510 (4.2%) | 1.23 (1.13 to 1.53) |
Homogeneity test (p-value) | 0.0448 | <0.0001 | ||||
Low birth weight | ||||||
Cephalosporins | 7816 (1.1%) | 411 (5.3%) | 1.10 (1.00–1.22) | 4675 (0.6%) | 217 (4.6%) | 1.26 (1.11 to 1.44) |
Penicillins | 84,211 (12.1%) | 4050 (4.8%) | 1.05 (1.01–1.08) | 52,923 (6.8%) | 1967 (3.7%) | 1.05 (0.99 to 1.09) |
Macrolides | 24,763 (3.6%) | 1347 (5.4%) | 1.17 (1.11–1.24) | 9316 (1.2%) | 462 (5.0%) | 1.33 (1.21 to 1.46) |
Fluoroquinolones | 6352 (0.9%) | 331 (5.2%) | 1.09 (0.97–1.21) | 1550 (2.2%) | 71 (4.6%) | 1.25 (0.99 to 1.58) |
Other | 24,715 (3.6%) | 1317 (5.3%) | 1.16 (1.09–1.23) | 13,885 (1.8%) | 534 (3.8%) | 1.05 (0.96 to 1.14) |
Homogeneity test (p-value) | 0.0026 | <0.0001 | ||||
Small for gestational age | ||||||
Cephalosporins | 7816 (1.1%) | 575 (7.4%) | 0.99 (0.92 to 1.09) | 4675 (0.6%) | 345 (7.4%) | 1.10 (0.99 to 1.22) |
Penicillins | 84,211 (12.1%) | 6045 (7.2%) | 0.97 (0.94 to 1.00) | 52,923 (6.8%) | 3696 (7.0%) | 1.00 (0.96 to 1.03) |
Macrolides | 24,763 (3.6%) | 1858 (7.5%) | 1.02 (0.97 to 1.07) | 9316 (1.2%) | 673 (7.2%) | 1.07 (0.99 to 1.15) |
Fluoroquinolones | 6352 (0.9%) | 466 (7.3%) | 0.99 (0.90 to 1.09) | 1550 (2.2%) | 126 (8.1%) | 1.15 (0.97 to 1.37) |
Other | 24,715 (3.6%) | 1864 (7.5%) | 1.03 (0.98 to 1.09) | 13,885 (1.8%) | 960 (6.9%) | 0.98 (0.92 to 1.05) |
Homogeneity test (p-value) | 0.2032 | 0.0971 | ||||
Low 5 min Apgar score | ||||||
Cephalosporins | 7816 (1.1%) | 50 (0.6%) | 1.33 (1.00 to 1.76) | 4675 (0.6%) | 16 (3.7%) | 0.84 (0.51 to 1.38) |
Penicillins | 84,211 (12.1%) | 417 (0.5%) | 1.07 (0.96 to 1.18) | 52,923 (6.8%) | 234 (0.4%) | 1.10 (0.96 to 1.26) |
Macrolides | 24,763 (3.6%) | 123 (0.5%) | 1.05 (0.88 to 1.26) | 9316 (1.2%) | 50 (0.5% | 1.35 (1.02 to 1.79) |
Fluoroquinolones | 6352 (0.9%) | 36 (0.6%) | 1.16 (0.83 to 1.61) | 1550 (2.2%) | 3 (0.2%) | 0.45 (0.14 to 1.40) |
Other | 24,715 (3.6%) | 151 (0.6%) | 1.32 (1.12 to 1.56) | 13,885 (1.8%) | 70 (0.5%) | 1.24 (0.97 to 1.57) |
Homogeneity test (p-value) | 0.1782 | 0.1961 |
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Cantarutti, A.; Rea, F.; Franchi, M.; Beccalli, B.; Locatelli, A.; Corrao, G. Use of Antibiotic Treatment in Pregnancy and the Risk of Several Neonatal Outcomes: A Population-Based Study. Int. J. Environ. Res. Public Health 2021, 18, 12621. https://doi.org/10.3390/ijerph182312621
Cantarutti A, Rea F, Franchi M, Beccalli B, Locatelli A, Corrao G. Use of Antibiotic Treatment in Pregnancy and the Risk of Several Neonatal Outcomes: A Population-Based Study. International Journal of Environmental Research and Public Health. 2021; 18(23):12621. https://doi.org/10.3390/ijerph182312621
Chicago/Turabian StyleCantarutti, Anna, Federico Rea, Matteo Franchi, Benedetta Beccalli, Anna Locatelli, and Giovanni Corrao. 2021. "Use of Antibiotic Treatment in Pregnancy and the Risk of Several Neonatal Outcomes: A Population-Based Study" International Journal of Environmental Research and Public Health 18, no. 23: 12621. https://doi.org/10.3390/ijerph182312621