Table 2

Risk factors for NEC and mortality using competing-risks Cox regression models (n=596)*

 Risk factor n (for NEC) n NEC Mortality CSHR (95% CI) P value CSHR (95% CI) P value A. Univariable analysis Postnatal CMV—TDC (early)†‡ 43 596 4.95 (1.08 to 22.6) 0.04 0¶ Postnatal CMV—TDC (midpoint)†§ 43 596 2.23 (0.54 to 9.20) 0.27 0¶ Birth weight (per 100 g increase) 43 596 0.75 (0.66 to 0.86) <0.001 0.52 (0.42 to 0.64) <0.001 Maximum CMV viral load in breast milk in first 14 days of life (per twofold increase or doubling) 43 596 1.37 (1.14 to 1.64) <0.001 0.81 (0.54 to 1.19) 0.28 Maximum CMV viral load in breast milk in first 14 days of life, excluding infants never fed (per twofold increase or doubling)** 43 540 1.32 (1.09 to 1.59) 0.004 0.83 (0.56 to 1.23) 0.34 Maximum CMV viral load in breast milk in first 14 days of life among infants fed CMV+breast milk (per twofold increase or doubling)** 26 259 1.35 (1.02 to 1.78) 0.03 0.85 (0.49 to 1.48) 0.57 Infant race (black vs non-black) 43 596 1.72 (0.90 to 3.28) 0.10 1.01 (0.41 to 2.50) 0.99 Mother’s age (per 1 year increase) 43 596 0.98 (0.93 to 1.04) 0.50 1.02 (0.95 to 1.09) 0.55 PROM (yes vs no) 43 595 0.53 (0.27 to 1.07) 0.07 2.20 (0.89 to 5.43) 0.09 B1. Multivariable (n=596) Postnatal CMV—TDC (midpoint)†§ 2.81 (0.73 to 10.9) 0.13 0¶ Birth weight (per 100 g increase) 0.75 (0.65 to 0.86) <0.001 0.52 (0.41 to 0.65) <0.001 B2. Multivariable (n=596) Postnatal CMV—TDC (early)†‡ 6.02 (1.28 to 28.4) 0.02 0¶ Birth weight (per 100 g increase) 0.75 (0.65 to 0.86) <0.001 0.52 (0.41 to 0.65) <0.001 B3. Multivariable (n=596) Postnatal CMV—TDC (early)† ‡ 3.94 (0.77 to 20.0) 0.10 0¶ Birth weight (per 100 g increase) 0.76 (0.67 to 0.88) <0.001 0.49 (0.38 to 0.62) <0.001 Maximum CMV viral load in breast milk in first 14 days of life (per twofold increase or doubling) 1.26 (1.05 to 1.52) 0.02 0.71 (0.48 to 1.03) 0.07 B4. Multivariable (n=596) Birth weight (per 100 g increase) 0.77 (0.67 to 0.88) <0.001 0.47 (0.36 to 0.62) <0.001 Maximum CMV viral load in breast milk in first 14 days of life (per twofold increase ordoubling) 1.28 (1.06 to 1.54) 0.01 0.73 (0.46 to 1.14) 0.17 Mother’s age (per 1 year increase) 1.00 (0.95 to 1.06) 0.78 1.00 (0.91 to 1.09) 0.97 Infant race (black vs non-black) 1.29 (0.64 to 2.57) 0.48 0.84 (0.34 to 2.12) 0.72 PROM (yes vs no) 0.55 (0.27 to 1.13) 0.10 2.26 (0.91 to 5.58) 0.08 B5. Multivariable (n=596) Birth weight (per 100 g increase) 0.75 (0.65 to 0.86) <0.001 0.49 (0.38 to 0.64) <0.001 Postnatal CMV—TDC (early)†‡ 8.45 (1.83 to 38.9) 0.006 0¶ Mother’s age (per 1 year increase) 1.00 (0.95 to 1.06) 0.93 1.02 (0.95 to 1.09) 0.65 Infant race (black vs non-black) 1.34 (0.68 to 2.65) 0.40 0.86 (0.33 to 2.20) 0.74 PROM (yes vs no) 0.48 (0.23 to 0.98) 0.04 2.49 (0.99 to 6.29) 0.05
• *Competing risks were 43 infants with NEC and 31 deaths total; 12 infants with NEC died and 19 deaths included in the mortality models. Two additional infants with congenital CMV infection were excluded (one infant diagnosed with NEC at age 15 days).

• †Postnatal CMV infection included as a dichotomous time dependent covariate that can change, at most, once from uninfected to infected over 12 weeks of follow-up that is, once exposed always exposed.

• ‡Onset of postnatal CMV defined as time of earliest positive NAT result.

• §Onset of postnatal CMV defined as the midpoint of last negative and first positive NAT result.

• ¶ Of 19 non-NEC deaths, zero infants had postnatal CMV infection. Of note, 12 infants with NEC died.

• **Fifty-six infants were not fed and were not included in the analysis.

• Note: All multivariable models include adjustment for centre (estimates not shown). Doubling the maximum CMV viral load in breast milk in the first 14 days of life corresponds to an increment of 1 in the log2 scale.

• CMV, cytomegalovirus; CSHR, cause specific HR; NAT,  nucleic acid testing; NEC,  necrotising  enterocolitis; TDC, time dependent covariate; PROM, premature rupture of membranes.