Abstract: Thirty-five trials involving 1,997 newborns were included. Thirty-three trials enrolled healthy, full term neonates, and two enrolled infants born preterm.   Fourteen trials involving 592 newborns compared dorsal penile nerve block (DPNB) with placebo or no treatment. Compared to placebo/no treatment, DPNB demonstrated significantly lower heart rate [WMD -35 bpm, 95% CI -41 to -30], decreased time crying [WMD -54 %, 95% CI -64 to -44], and increased oxygen saturation [WMD 3.7 %, 95% CI 2.7 to 3.7]. Six trials involving 200 newborns compared eutectic mixture of analgesics (EMLA) with placebo. EMLA demonstrated significantly lower facial action scores [WMD -46.5, 95% CI -80.4 to -12.6], decreased time crying [WMD - 15.2 %, 95% CI -21 to -9.3] and lower heart rate [WMD -15 bpm, 95% CI -19 to -10]. DPNB, compared with EMLA in three trials involving 139 newborns (133 of whom were included in the analysis), demonstrated significantly lower heart rate [WMD -17 bpm, 95% CI -23 to -11] and pain scores. When compared with sucrose in two trials involving 127 newborns, DPNB demonstrated less time crying [MD -166 s, 95% CI -211 to -121], and lower heart rate [WMD -27 bpm, 95% CI -33 to -20]. Results obtained for trials comparing oral sucrose and oral analgesics to placebo, and trials of environmental modification were either inconsistent or were not significantly different. Adverse effects included gagging, choking, and emesis in placebo/untreated groups. Minor bleeding, swelling and hematoma were reported with DPNB. Erythema and mild skin pallor were observed with the use of EMLA. Methaemoglobin levels were evaluated in two trials of EMLA, and results were within normal limits. DPNB was the most frequently studied intervention and was the most effective for circumcision pain. Compared to placebo, EMLA was also effective, but was not as effective as DPNB. Both interventions appear to be safe for use in newborns. None of the studied interventions completely eliminated the pain response to circumcision.

Plain-language summary: Based on 35 clinical trials involving 1,997 newborns, it can be concluded that DPNB and EMLA do not eliminate circumcision pain, but are both more effective than placebo or no treatment in diminishing it. Compared head to head, DPNB is substantially more effective than EMLA cream. Ring block and lidocaine creams other than EMLA also reduced pain but did not eliminate it. Trials of oral acetaminophen, sugar solutions, pacifiers, music, and other environmental modifications to reduce circumcision pain did not prove them effective. DPNB can cause minor bruising, bleeding, or swelling at the injection site. EMLA and other lidocaine creams can cause skin color changes or local skin irritation. There is a rare risk with lidocaine creams of causing methaemoglobinaemia (blue-baby syndrome, where the baby's blood lacks sufficient oxygen). However, two trials of EMLA for circumcision pain relief measured methaemoglobin levels and found them normal. The circumcision procedure itself, especially without pain relief, can cause short term effects such as choking, gagging, and vomiting. Long term effects of circumcision without pain relief are not well understood. Strict comparability between trials was rare. Trials used a variety of indicators to measure baby's pain. Crying time, facial expression, and sweating palms can indicate infant pain, as can increased heart rate, breathing rate, and blood pressure. Levels of chemical indicators that can be part of a pain or stress response and are present in the blood or saliva are another gauge of pain levels. Also, procedures were not generally performed in just the same way in different trials. Type of clamp used (8sing a Mogen clamp can shorten the duration of the procedure), length of wait time after injection or application of anesthetic and procedure techniques varied.