Table 1 Assessment across the statistically significant associations for preterm birth

Robust

 > 1000 cases, ^a P < 10⁻⁶, not large heterogeneity (I² < 50%), 95% prediction interval excluding the null value, no evidence for small-study effects^b, and excess significance bias ^c

 Risk factors supported by robust evidence

Amphetamines [53]

Isolated single umbilical artery [60]

Maternal personality disorder [70]

SDB (objective assessment) [80]

Prior I-TOP with VA [98]

Low GWG [107]

IPI following miscarriage of < 6 m (compared to IPI following miscarriage of ≥ 6 months, with Conde-Agudelo A, 2004 excluded) [108]

Highly Suggestive

 > 1000 cases, ^a P < 10⁻⁶ and statistically significant effect present at the largest study at P < 0.05

 Risk factors supported by highly suggestive evidence

1^st trimester bleeding [51]

Prior surgical I-TOP (for PTB in singleton pregnancies) [98]

Obstetric cholestasis [66]

PCOS [115]

Cancer survivors [41]

Placenta previa [43]

African/Black race [49]

Aboriginal ethnicity [50]

BMI of > 40 kg/m² (compared to BMI = 30–34.9 kg/m²) [75]

BMI of > 40 kg/m² (compared to BMI = 30–39.9 kg/m²) [75]

Endometriosis (combined spontaneous conception and assisted reproduction) [8]

Endometriosis (spontaneous conception) [8]

Maternal age of ≥ 45 years old [103]

CKD during pregnancy [104]

Underweight women [105]

Maternal vitamin D status (for spontaneous PTB) [110]

SMM: hemorrhagic disorders [68]

SMM: hepatic disorders [68]

LEEP [111]

LLETZ for CIN [112]

Any type of treatment for CIN with a cone depth of ≥ 10–12 mm (compared to untreated CIN) [112]

Any type of treatment for CIN with a cone depth of ≥ 15–17 mm (compared to untreated CIN) [112]

Intimate partner violence [39]

Unmarried women [52]

Cocaine [79]

Entire pregnancy high level PM_2.5 exposure [48]

Suggestive

 > 1000 cases, ^a P < 10⁻³

 Risk factors supported by suggestive evidence

Pre-gravid OC use [40]

Marijuana during pregnancy [57]

SMM: thromboembolic disorders [68]

Periodontal disease [74]

Women of short stature [77]

Antipsychotics during pregnancy [38]

Trichomonas vaginalis infection [84]

Blastocyst-stage embryo transfer (vs cleavage embryo transfer) [86]

Fresh blastocyst transfer (for PTB) [89]

Fresh blastocyst transfer (for very PTB < 32 weeks) [89]

HPV Infection (crude) [7]

HPV Infection (age adjusted) [7]

 > 1 prior surgical I-TOP [98]

Any type of treatment for CIN with a cone depth of ≥ 20 mm (compared to untreated CIN) [112]

Greenery (including only a 100-m NDVI buffer) [113]

Weak

The rest associations with^aP < 0.05

 Risk factors supported by weak evidence

History of preterm twins [4]

History of preterm twins 34–36 + 6 weeks [4]

History of preterm twins 30–33 + 6 weeks [4]

History of preterm twins < 30 weeks [4]

History of spontaneous twin preterm birth [4]

History of spontaneous twin preterm birth 34–36 + 6 weeks [4]

Subseptate uterus [46]

Cancer survivors treated after radiotherapy [41]

H1 Antihistamine [37]

Velamentous cord insertion [42]

Metformin [44]

Diabetic nephropathy in T1DM [45]

Preconception care [47]

Asian race [49]

Hispanic ethnicity [49]

Laparoscopic appendectomy [9]

Hyperemesis gravidarum (cohort studies) [54]

Hyperemesis gravidarum (case control studies) [54]

Arcuate uterus [46]

Septate uterus [46]

Bicornuate uterus [46]

Didelphys uterus [46]

Unicornuate uterus [46]

Triptan [55]

Migraine [55]

Topical retinoids (exposed infants) [56]

Hydroxychloroquine [56]

TB [58]

Multivitamins [59]

Fetus with small thymus [61]

Probiotics during pregnancy (for PTB < 34 weeks) [62]

Probiotics during pregnancy (for PTB < 37 weeks) [62]

Home visits for pregnant women [63]

APS [64]

Bed Rest (in developing regions, for PTB < 37 weeks) [65]

Bed Rest (in developed regions, for PTB < 37 weeks) [65]

Bed Rest (in developing regions, for very PTB) [65]

Bed Rest (in developed regions, for very PTB) [65]

Pregnancy-associated malaria [67]

Nicotine Replacement Therapy [69]

Women involved in motor vehicle crashes [71]

Magnesium supplementation [72]

Donor sperm (for PTB) [73]

Donor sperm (for very PTB) [73]

Bariatric surgery [76]

Vitamin C and others supplementation [78]

SDB (questionnaire-based assessment) [80]

Asthma with exacerbation during pregnancy [81]

Asthma without exacerbation during pregnancy [81]

Alcohol consumption before or during pregnancy [83]

Vaginal clindamycin treatment for bacterial vaginosis [85]

Single embryo transfer (randomized clinical trials) [87]

Single embryo transfer (cohort studies) [87]

Stimulated cycle IVF [88]

Bacterial vaginosis [90]

Intermediate vaginal flora [90]

HPV 6/11/16/18 vaccine in periconceptional period or during pregnancy [6]

Quinolones during 1st trimester [91]

Macrolides [92]

Clindamycin [92]

Metronidazole alone or in combination [92]

Metronidazole [92]

Dental caries [93]

Celiac disease [94]

Single-twin death after 14 weeks of monochorionic pregnancy [95]

Prenatal care (observational studies) [96]

Prenatal care (randomized clinical trials) [96]

Endometriosis (assisted reproduction) [8]

Knowledge of TVU-measured CL in singletons pregnancies with symptoms of PTL [97]

Only 1 prior surgical I-TOP [98]

Prior 1st trimester surgical I-TOP [98]

Prior S-TOP [98]

Prior uterine evacuation [98]

Prior I-TOP [98]

Prior I-TOP with dilation and evacuation [98]

Hyperthyroidism [99]

Clinical hypothyroidism [100]

Subclinical hypothyroidism [100]

Hypothyroxinemia [100]

LT4 treatment in euthyroid women with thyroid autoimmunity (with Negro R, 2016 included) [101]

LT4 treatment in euthyroid women with thyroid autoimmunity (with Negro R, 2016 excluded) [101]

Primiparous mother [102]

High GWG [106]

IPI following miscarriage of < 6 months (compared to IPI following miscarriage of ≥ 6 months,

with Conde-Agudelo A, 2004 included) [108]

IPI following miscarriage < 6 months (compared to IPI following miscarriage of 6–12 months) [108]

IPI following miscarriage < 6 months (compared to IPI following miscarriage of > 12 months) [108]

Treated CIN (for PTB < 37 weeks) [109]

Treated CIN during pregnancy [109]

Treated CIN before pregnancy [109]

Untreated CIN [109]

Treated CIN (for spontaneous PTB < 37 weeks) [109]

Treated CIN (for PTB < 32 weeks) [109]

maternal 25-OHD concentration of < 50 nmol/L [110]

maternal 25-OHD concentration of < 75 nmol/L [110]

Vitamin D supplementation [110]

Maternal Vitamin D status (for PTB in general) [110]

Any type of treatment for CIN with a cone depth of ≤ 10–12 mm (compared to untreated CIN) [112]

Any type of treatment for CIN with a cone depth of ≥ 10–12 mm (compared to any type of treatment for CIN with a cone depth of ≤ 10–12 mm) [112]

Any type of treatment for CIN with a cone depth of ≥ 15–17 mm (compared to any type of treatment for CIN with a cone depth of ≤ 15–17 mm) [112]

Any type of treatment for CIN with a cone depth of ≥ 20 mm (compared to any type of treatment for CIN with a cone depth of ≤ 20 mm) [112]

1st trimester PM_2.5 exposure [48]

Entire pregnancy PM_2.5 exposure [48]

1st trimester high-level PM_2.5 exposure [48]

1st trimester low level PM_2.5 exposure [48]

Entire pregnancy low level PM_2.5 exposure [48]

Entire pregnancy PM_2.5 exposure [114]

1^st trimester PM_2.5 exposure [114]

2^nd trimester PM_2.5 exposure [114]

3^rd trimester PM_2.5 exposure [114]

1^st month PM_2.5 exposure [114]

Within 1 month before birth PM_2.5 exposure [114]

Individual-level PM_2.5 exposure [114]

Semi-individual-level PM_2.5 exposure [114]

Regional-level PM_2.5 [114]

PM_2.5 exposure [114]

1^st trimester NO₂ exposure [82]

2^nd trimester NO₂ exposure [82]

3^rd trimester NO₂ exposure [82]

Whole pregnancy NO₂ exposure [82]