Maternal caffeine intake during pregnancy and risk of pregnancy loss: a categorical and dose-response meta-analysis of prospective studies.
OBJECTIVE
To assess the association between maternal caffeine intake and risk of pregnancy loss using a systematic review and meta-analysis.


METHODS
Categorical and dose-response meta-analysis of prospective studies.


METHODS
Relevant articles were identified by searching MEDLINE and SCOPUS databases through 30 January 2015. Two authors independently extracted information from eligible studies. Random-effects models were used to derive the summary relative risks (RR) and corresponding 95% CI for specific categories of caffeine consumption and for a continuous association using generalized least-squares trend estimation.


METHODS
A total of 130 456 participants and 3429 cases in fourteen included studies.


RESULTS
Compared with the reference category with no or very low caffeine intake, the RR (95% CI) of pregnancy loss was 1·02 (0·85, 1·24; I(2)=28·3%) for low intake (50-149 mg/d), 1·16 (0·94, 1·41; I 2=49·6%) for moderate intake (150-349 mg/d), 1·40 (1·16, 1·68; I(2)=18·6%) for high intake (350-699 mg/d) and 1·72 (1·40, 2·13; I(2)=0·0%) for very high intake (≥ 700 mg/d). In the dose-response analysis, each 100 mg/d increment in maternal caffeine intake (~1 cup of coffee) was associated with 7% (95% CI 3%, 12%) higher risk of pregnancy loss. Our results may have been affected by publication bias, but the association remained significant for the subset of larger studies. Furthermore, adjustment for smoking and pregnancy symptoms may have been incomplete, potentially resulting in residual confounding.


CONCLUSIONS
Albeit inconclusive, higher maternal caffeine intake was associated with a higher risk of pregnancy loss and adherence to guidelines to avoid high caffeine intake during pregnancy appears prudent.
1Saw Swee Hock School of Public Health,National University of Singapore and National University Health System,Tahir Foundation Building,12 Science Drive 2,Level 10,#10-01,Singapore 117549.
Ling-Wei
LW
Chen
1Saw Swee Hock School of Public Health,National University of Singapore and National University Health System,Tahir Foundation Building,12 Science Drive 2,Level 10,#10-01,Singapore 117549.
Yi
Y
Wu
1Saw Swee Hock School of Public Health,National University of Singapore and National University Health System,Tahir Foundation Building,12 Science Drive 2,Level 10,#10-01,Singapore 117549.
Nithya
N
Neelakantan
2Department of Paediatrics,Yong Loo Lin School of Medicine,National University of Singapore and National University Health System,CRC,MD11,10 Medical Drive,Level 1,#01-08,Singapore 117597.
Mary Foong-Fong
MF
Chong
1Saw Swee Hock School of Public Health,National University of Singapore and National University Health System,Tahir Foundation Building,12 Science Drive 2,Level 10,#10-01,Singapore 117549.
An
A
Pan
1Saw Swee Hock School of Public Health,National University of Singapore and National University Health System,Tahir Foundation Building,12 Science Drive 2,Level 10,#10-01,Singapore 117549.
Rob M
RM
van Dam
D000022:Abortion, Spontaneous / Q000453:epidemiology*; D002110:Caffeine / Q000008:administration & dosage* / Q000009:adverse effects*; D003069:Coffee / Q000009:adverse effects / Q000737:chemistry; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D011247:Pregnancy; D012307:Risk Factors
D003069:Coffee; D002110:Caffeine
Caffeine; Coffee; Miscarriage; Pregnancy; Pregnancy loss; Spontaneous abortion; Stillbirth