1. Objectives

To evaluate the effects of a restricted maternal caffeine intake on fetal, neonatal and pregnancy outcomes

2. How studies were identified

The following databases were searched in January 2015:

• Cochrane Pregnancy and Childbirth Group’s Trials Register
• CENTRAL (The Cochrane Library 2015)
• MEDLINE
• Embase
• CINAHL

Reference lists were also hand-searched and the authors directly contacted researchers

3. Criteria for including studies in the review

3.1 Study type

Randomized controlled trials, including cluster-randomized trials and quasi-randomized trials

3.2 Study participants

Pregnant women of any age and parity

3.3 Interventions

Caffeine intake or caffeine supplements during pregnancy in comparison with limited intake of caffeine or a placebo

(Caffeine intake included all caffeinated beverages, such as coffee and tea, and caffeinated non-beverages, such as chocolate and medications)

3.4 Primary outcomes

Fetal outcomes

• Birth weight (g)
• Low birth weight (<2500 g), very low birth weight (<1500 g), extremely low birth weight (<1000 g)
• Small-for-gestational age (<10^th centile for gestational age, assessed at time of birth)
• First trimester fetal loss or miscarriage (spontaneous end of pregnancy at <20 weeks’ gestation)
• Perinatal mortality rate per 100,000
• Fetal hypoxia
• Fetal tachycardia and arrhythmias
• Preterm birth before 37 weeks’ gestation

Secondary outcomes for the neonate included caffeine withdrawal syndrome, apnoea, tachycardia and arrhythmias, cerebral palsy and cognitive impairment, and sudden infant death syndrome. Secondary outcomes for the mother included headache, nausea, psychological outcomes, gestational diabetes mellitus, and glucose tolerance

4. Main results

4.1 Included studies

Two randomized controlled trials, involving 1234 women, were included in this review

• Only one study, enrolling 1207 women, contributed data for analysis
• Women who drank three cups of coffee per day were recruited at <20 weeks’ gestation
• Drinking three cups of decaffeinated instant coffee per day was compared to drinking the same volume of caffeinated instant coffee
• The women drinking decaffeinated coffee reduced their caffeine intake by a mean of 182 mg/day during the second and third trimesters

4.2 Study settings

• Canada (did not contribute data), and Denmark (contributed data)
• The Danish trial was conducted in a university hospital obstetrics department

4.3 Study settings

How the data were analysed
Pregnancy outcomes in the caffeinated group were compared to pregnancy outcomes in the decaffeinated group. Dichotomous data were presented as risk ratios (RR) with corresponding 95% confidence intervals (CI), while continuous data were presented as mean differences (MD) with corresponding 95% CI.

Results
Birth weight and small-for-gestational age
No significant difference in birth weight (MD 20 g, 95% CI [-48.68 to 88.68], 1197 participants), or in the number of infants born small-for-gestational age (RR 0.97, 95% CI [0.57 to 1.64], 1150 participants) was observed between the caffeinated and decaffeinated groups.

Preterm birth
The risk of preterm birth did not differ between caffeinated and decaffeinated groups (RR 0.81, 95% CI [0.48 to 1.37], 1153 participants).

No other pre-specified outcomes were reported on.

5. Additional author observations*

The overall risk of bias was low for the study contributing data to the review. However, GRADE quality of evidence assessments for the outcomes birth weight and preterm birth were rated as low due to the comparatively small sample size and wide CI.

Little evidence on the effect of caffeine on fetal, neonatal and maternal outcomes currently exists, and many pre-specified outcomes were not evaluated in the single trial included in this review. Further high-quality randomized controlled trials are needed in which a broader range of outcomes, such as those specified in this review, are investigated.