Mind the “CRP gender gap”! Sex differences in CRP evolution over time in neonatal sepsis: a monocentric retrospective cohort study

Mind the “CRP gender gap”! Sex differences in CRP evolution over time in neonatal sepsis: a monocentric retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Mind the “CRP gender gap”! Sex differences in CRP evolution over time in neonatal sepsis: a monocentric retrospective cohort study Andrea Nebbioso, Isaline Eggermont, Alfredo Vicinanza, Phu-Quoc Lê, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7573907/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background C-reactive protein (CRP) is a readily available test widely used to assess neonatal sepsis (NS). In children with sepsis or other infectious conditions, CRP is more likely to be higher in females than males, however, evidence is lacking on sex differences in CRP in the neonatal population. This study aims to describe sex differences of CRP evolution in the ascending and decreasing phase after its peak in neonates with clinical NS. Methods This is a monocentric retrospective cohort study conducted at Etterbeek-Ixelles Hospital in Brussels. We included all neonates born in the facility between January 2017 and December 2022 who received antibiotics in the first 72 hours of life. Patients whose CRP concentrations remained under 10 mg/L were excluded. To describe the ascending kinetics of CRP and its logarithm for male and female neonates, we fitted a piecewise linear mixed-effects regression model with birth considered as time zero and one knot at 12 hours of life. We used a linear mixed-effects regression model with CRP peak considered as time zero to describe CRP's descending kinetics and its logarithm for male and female neonates. Results We included 506 neonates (60.1% male and 39.9% female). CRP concentration in the first 12 hours of life doubled every 3.1 and 2.8 hours, respectively, in males and females, with female neonates having a statistically significant faster rise of base 2 logarithm of CRP (+ 0.037/hour 95% CI = + 0.014 + 0.061). After 12 hours of life, CRP doubled every 6.8 and 9.1 hours, respectively, in males and females, with female neonates having a statistically significant slower rise of base 2 logarithm of CRP (-0.038/hour 95% CI= -0.011 -0.064). After its peak, CRP decreased by half every 31.1 and 30.9 hours, respectively, for males and females. Conclusion In neonates of both sexes with clinical early-onset NS, CRP seems to increase, reach a peak, and then decrease, following a logarithmic pattern. Before antibiotic treatment, female neonates in our population had a statistically significant earlier increase in CRP levels, with no significant difference in the peak levels of CRP. CRP neonatal sepsis neonatal infection neonatal inflammation inflammation sex differences sexual dimorphism Figures Figure 1 Figure 2 BACKGROUND Neonatal sepsis (NS) has been defined as a systemic condition of infectious origin, resulting in substantial morbidity and mortality in neonates [ 1 ]. Most authors consider the first 72 hours of life the cut-off between early and late-onset NS, while others refer to late-onset NS (LONS) as occurring after seven days of life [ 1 ]. When cultures are negative, but the infants manifest signs consistent with infection, they may be considered to have “clinical NS” [ 2 ]. C-reactive protein (CRP) is the most widely used and readily available laboratory test to assess NS [ 3 ]. Two CRP values < 10 mg/L obtained 24 hours apart have very high specificity and, therefore, strong power in excluding early onset NS (EONS) [ 4 ]; however, once the clinician faces the opposite situation (one CRP measurement > 10 mg/L), CRP cut-offs multiply and sensitivity drops below 70% [ 5 ]. Previous studies demonstrated that CRP values of healthy neonates are log-normally distributed and physiologically rise in the first 24 hours of life starting from a very low level at birth [ 6 ] as CRP does not pass through placenta [ 7 ]. No sex differences in neonatal CRP levels have been found in a healthy neonatal population [ 6 ]. Many studies focused on the specificity and sensibility of CRP at specific times for the diagnosis of NS [ 5 ]. The evolution of CRP over time in neonates with NS or other inflammatory conditions has been poorly described. One study, with different primary goals, accidentally described CRP values over time in neonates with NS with few cases of confirmed NS, mostly in preterm, with only 4 cases of term neonates [ 8 ]. No study has been published describing CRP values over time after antibiotic treatment in the neonatal population. The CRP decrease pattern over time after its initial peak has been described mainly in the adult population with an estimated half-life of 19 hours [ 9 ]. We found no neonatal-specific data assessing CRP half-life after its peak. Increasing evidence suggest that overlooking sex differences in research leads to poorer outcomes for females [ 10 , 11 ]. A large epidemiological study on severe sepsis in children in the United States confirmed that being male is a risk factor for worse outcomes in cases of prematurity and some neonatal infections [ 12 ]. Moreover, a genome-wide association study with 224 LONS cases showed that genetic susceptibility to LONS exhibits sexual dimorphism, with NOTCH signaling playing a role in determining the associated risk [ 13 ]. In children with sepsis or other infectious conditions, CRP values are more likely to be higher in females than males [ 14 , 15 ]. In the early stage of the infection, inflammatory biomarkers are more elevated in females, indicating a stronger immune activation. Over time, a distinct kinetic pattern emerges between sexes in the return to homeostasis. In contrast, levels of proinflammatory cytokines, such as interleukin (IL) 1β, IL-6, and tumor necrosis factor-alpha (TNF-α), are higher in men, whereas women exhibit elevated levels of anti-inflammatory mediators, notably IL-10 [ 16 , 17 ]. This study aims to determine whether there are sex-based differences in CRP kinetics over time during the early neonatal period in neonates with clinical NS. Our objective is to provide sex-based differential references describing how CRP rises before and stabilizes after antibiotic treatment and how quickly CRP decreases after its peak. METHODS Study design and setting. This is a monocentric retrospective cohort study conducted in the neonatal unit (NU) and maternity ward (MW) of Etterbeek-Ixelles Hospital (EIH). We included all neonates born in the facility between January 2017 and December 2022 and treated with antibiotics. We excluded patients who started antibiotic therapy after 72 hours of life. Patients whose CRP concentrations remained under 10 mg/L during the hospital stay were also excluded. Only blood samples realized in EIH were considered in the analysis of patients who had to be transferred to other centers. EIH MW has an average of 2000 live births/year, and the NU has an admission rate of approximately 400 patients/year with a multi-ethnic patient population. Neonates treated with antibiotics in EIH MW are systematically admitted for the first few hours in the NU. As EIH NU provides sub-intensive neonatal care, preterm neonates before 32 weeks of gestational age are transferred to larger centers, as well as neonates with a birth weight under 1500 grams. EIH NU has incubators and can provide non-invasive ventilation, oxygen therapy, parenteral nutrition via central lines and nasogastric tube feeding. In EIH NU and MW, the first-line treatment of NS is a combination of amoxicillin-amikacin (5 days of amoxicillin and 2 days of amikacin), and the second-line treatment consists of the association of amoxicillin-cefotaxime. The tool of the neonatal sepsis risk calculator, as developed by Kuzniewicz et al., [ 18 – 21 ] has been systematically used to assess the NS risk since January 2020. In EIH NU and MW, CRP is measured before antibiotic treatment at 0, 12, and 24 hours of life in the presence of infectious risk factors. CRP is systematically measured 12 and 30 hours after antibiotic treatment. Data Collection and statistical analysis . Patients’ files were retrospectively reviewed to collect the data. The following information was collected: date of birth, birth weight and its Z-score, gestational age at birth, sex, type of delivery, presence of risk factors for NS (meconial liquid, maternal fever, prolonged membrane rupture, maternal group B streptococcus colonization, chorioamnionitis and maternal antibiotic treatment), data about clinical presentation of neonates (fever, jaundice, respiratory distress, time of antibiotic start and blood culture result), CRP values and time of sampling. Frequencies and proportions were calculated for categorical variables. Fisher exact test was used to determine the association between categorical variables. Continuous variables were described using the median and interquartile range. Mann-Whitney test was performed for continuous variables. By convention, we decided to express time in hours and CRP in mg/L. We will refer to “base 2 CRP logarithm” (CRPlog2) as the base 2 logarithm of CRP values expressed in mg/L. We decided to describe CRP and CRPlog2 kinetic according to three different time axes. The first axis of time considers birth as time 0 and aims to describe the ascending phase of CRP and CRPlog2 before antibiotic start. The second axis of time considers antibiotic start as time 0 and seeks to describe the ascending-descending transition phase. The third axis of time designates time 0 as the point at which CRP peaks and aims to describe the subsequent descending phase. We fitted two identical models (one for CRP and one for CRPlog2) for each time axis. To describe the ascending kinetics of CRP and CRPlog2 for male and female neonates, we fitted a piecewise linear mixed-effects regression model where birth was considered as time zero with one knot at 12 hours of life, with observations occurring after 24 hours of life or after antibiotic treatment being excluded. Sex was the only covariate in this model. To describe the transition of CRP and CRPlog2 from ascending to descending phase, we fitted a piecewise linear mixed-effects regression model where antibiotic treatment start was considered as time zero with one knot at 12 hours of antibiotic treatment and observations occurring before antibiotic treatment or 30 hours after were excluded. Sex and time of antibiotic start (at birth vs after birth) were the two covariates in this model. To describe the descending kinetics of CRP and CRPlog2 for male and female neonates, we fitted a linear mixed-effects regression model where the CRP peak was considered as time zero, with observations occurring before the CRP peak or 120 hours after being excluded. Sex was the only covariate in this model. In all fitted models, we introduced a random effect on intercepts and slopes and we used the restricted maximum likelihood method to calculate standard error. We used an unstructured covariance matrix for serial correlation for all fitted models. A p-value of < 0.05 was considered statistically significant. Statistical analyses were performed using STATA version 15.1 for MacOS (StataCorp, College Station, Texas 77845 USA). Ethics approval and consent to participate The study protocol was approved by the ethics committee of EIH MW (CE/2024 – 01) and the reported investigations were carried out in accordance with the principles of the Declaration of Helsinki as revised in 2013. Results During the study period, 506 neonates met the inclusion criteria, with 304 males (60.1%) and 202 females (39.9%). Table 1 summarizes the population's general demographic and clinical characteristics according to sex. In our population, 2.6% of neonates were born preterm, and 2.8% presented with a low birth weight. Treatment was started at birth in 29.4% of cases. Male neonates presented more frequently jaundice (12% vs 6.5%, p-value 0.047). We had no neonate with positive blood culture or fatal outcome. [Insert Table 1] Table 2 shows the evolution of CRP and its base 2 logarithm before antibiotic treatment, in the first 12 hours of life and from 12 to 24 hours of life. At time 0 (birth) both sexes had mean CRP values statistically different from 0 (2.18; 95% CI= 1.41 2.94 for males and 2.34; 95% CI 1.41 3.27 for females) with no statistically significant difference between sexes. In both sexes CRP level rose in the first 12 hours of life (0.91/hour; 95% CI= 0.78 1.04 for males and 1.24/hour; 95% CI= 1.09 1.4 for females). Female neonates had a statistically significant faster rise in CRP (+ 0.34/hour; 95% CI= 0.13 0.54) compared to males. From hour 12 to hour 24 of life, CRP had a more rapid rise in both sexes (2.06/hour; 95% CI=1.92 2.21 for males and 1.91/hour; 95% CI= 1.72 2.1 for females) with no statistically significant difference between sexes. Figure 1 graphically represents these findings in its left part. Table 1. General characteristics of neonates with CRP rise higher than 10 mg/L admitted to Ixelles neonatal unit (Bruxelles, Belgium) from January 2017 to December 2022. Males (n=304) Females (n=202) Total (n=506) Fisher’s exact/ Mann-Whitney test p-value Neonatal characteristics Gestational age (n=506) Late preterm (32-37 weeks) 10 (3.3%) 3 (1.5%) 13 (2.6%) 0.17 Term (>37 weeks) 294 (96.7%) 199 (98.5%) 493 (97.4%) Gestational age weeks (median p25 p75) 40 (39 41) 40 (39 41) 40 (39 41) 0.58 Birth weight (n=506) Low birth weight (1.5-2.5 kg) 11 (3.6%) 3 (1.5%) 14 (2.8%) 0.17 Normal birth weight (>2.5 kg) 293 (96.4%) 199 (98.5%) 492 (97.2%) Birth weight Kg (median p25 p75) 3.6 (3.23 3.86) 3.43 (3.16 3.73) 3.52 (3.2 3.8) 0.006 Birth weight Z-score (median p25 p75) 0.10 (-0.48 0.79) 0.16 (-0.5 0.81) 0.12 (-0.48 0.79) 0.34 Clinical characteristics Respiratory distress (n=499) 65 (21.7%) 44 (22.1%) 109 (21.8%) 0.91 Jaundice (n=499) 36 (12.0%) 13 (6.5%) 49 (9.8%) 0.047 Fever (n=503) 28 (9.3%) 19 (9.4%) 47 (9.3%) 1.0 Treatment started at birth (n=506) 86 (28.3%) 63 (31.2%) 149 (29.4%) 0.49 Positive blood culture (n=506) 0 (0%) 0 (0%) 0 (0%) 1.0 Contaminant positive blood culture (n=506) 7 (2.3%) 4 (2.0%) 11 (2.2%) Delivery characteristics Delivery type (n=506) Vaginal 141 (34.9%) 99 (49.0%) 240 (47.4%) 0.76 Vacuum-assisted 106 (46.4%) 70 (34.7%) 176 (34.8%) Caesar i an 57 (18.7%) 33 (16.3%) 90 (17.8%) Infectious risk factors Maternal fever (n=491) 56 (19.0%) 44 (22.3%) 100 (20.4%) 0.42 Maternal chorioamnionitis (n=500) 8 (2.7%) 2 (1.0%) 10 (2.0%) 0.33 Prolonged membrane rupture (>18 h) (n=490) 68 (23.0%) 38 (19.5%) 106 (21.6%) 0.37 Meconial amniotic liquid (n=476) 113 (39.5%) 87 (45.8%) 200 (42.0%) 0.18 Maternal antibiotic treatment (n=499) 154 (51.5%) 86 (43.0%) 240 (48.1%) 0.07 GBS colonisation (n=482) 84 (29.2%) 42 (21.6%) 126 (26.1%) 0.07 [Insert Figure 1] For CRPlog2 the pattern was quite similar with no statistically significant difference between sexes at birth and with both sexes having a mean CRPlog2 level different from 0 (-0.55; 95% CI=-0.75 -0.36 for males and -0.51; 95% CI= -0.75 -0.28 form females). In the first 12 hours, both sexes had a statistically significant rise in CRPlog2 (0.32/hour; 95% CI= 0.31 0.34 for males and 0.36/hour; 95% CI=0.34 0.38 for females) with a statistically significant faster rise of CRPlog2 in females (+0.037/hour 95% CI= 0.014 0.061). From hour 12 to hour 24 both sexes had a statistically significant rise in CRPlog2 (0.15/hour; 95% CI= 0.13 0.16 for males and 0.11/hour; 95% CI=0.09 0.13 for females) with a less rapid rise of CRPlog2 in females (-0.038/hour 95% CI= -0.064 -0.011). This means that, in our population, CRP plasma concentrations in the first 12 hours of life doubled every 3.1 hours for male neonates and every 2.8 hours for female neonates. Therefore, after the 12 th hour of life it took 6.8 hours for male neonates and 9.1 hours for female neonates, to double CRP plasma concentrations. Figure 2 graphically represents these findings in its left part. [Insert Figure 2] Table 3 shows the different evolutions of CRP levels and its base 2 logarithm after antibiotic treatment, according to sex and the timing of antibiotic treatment (started at birth vs not); slopes are described in the first 12 hours of antibiotic treatment and afterward, up to 30 hours from antibiotic start. For neonates with antibiotics started at birth, at time 0 (antibiotic start and birth), both sexes had mean CRP values different from 0 (4.49; 95% CI= 2.02 6.47 for males and 5.36; 95% CI 2.46 8.26 for females). In both sexes, CRP levels rose in the first 12 hours of antibiotic treatment (1.74/hour; 95% CI= 1.4 2.09 for males and 1.74/hour; 95% CI= 1.35 2.14 for females). From hour 12 to hour 30 of antibiotic treatment, CRP kept rising at a less rapid rate in both sexes (0.39/hour; 95% CI= 0.23 0.54 for males and 0.34/hour; 95% CI= 0.16 0.53 for females). On the other hand, for neonates with antibiotics started after birth, at time 0 (antibiotic start), both sexes had mean CRP values statistically different from 0 (32.28; 95% CI= 30.72 33.84 for males and 33.27; 95% CI 31.32 35.23 for females), but these values were considerably higher than those of the neonates who received antibiotics at birth. Unlike neonates treated at birth, those treated after birth had CRP levels that remained stable in the first 12 hours of antibiotic treatment (0.025/hour; 95% CI= -0.82 0.24 for males and 0.27/hour; 95% CI= 0.001 0.54 for females) and from hour 12 to hour 30 of antibiotic treatment, CRP levels started to decrease (-0.71/hour; 95% CI= -0.81 -0.62 for males and -0.80/hour; 95% CI= -0.92 -0.68 for females). We found no statistically significant difference between sexes in both groups (antibiotics started at birth or after), neither in intercepts nor in slopes. Figure 1 graphically represents these findings in its middle part. Regarding neonates with antibiotics started at birth, at time 0 (antibiotic start and birth), CRPlog2 values were not statistically different from 0 (0.22; 95% CI= -0.054 0.49 for males and 0.28; 95% CI -0.04 0.60 for females). In both sexes, CRPlog2 rose in the first 12 hours of antibiotic treatment (0.32/hour; 95% CI= 0.30 0.34 for males and 0.33/hour; 95% CI= 0.30 0.35 for females). From hour 12 to hour 30 of antibiotic treatment, CRPlog2 kept rising with a less rapid rate in both sexes (0.033/hour; 95% CI= 0.026 0.041 for males and 0.027/hour; 95% CI= 0.018 0.036 for females). On the other hand, for neonates with antibiotics started after birth, at time 0 (antibiotic start) both sexes had mean CRPlog2 values statistically different from 0 (4.9; 95% CI= 4.73 5.07 for males and 4.97; 95% CI 4.75 5.18 for females) and much higher compared to the neonates with antibiotics started at birth. Unlike neonates treated at birth, in those treated after birth, CRPlog2 remained stable in the first 12 hours of antibiotic treatment (-0.004/hour; 95% CI= -0.02 0.01 for males and -0.0015/hour; 95% CI= -0.02 0.014 for females) and from hour 12 to hour 30 of antibiotic treatment, CRPlog2 started to decrease (-0.04/hour; 95% CI= -0.045 -0.035 for males and -0.04/hour; 95% CI= -0.047 -0.035 for females). In both groups (antibiotic started at birth or after), we found no statistically significant difference between sexes, neither in intercept nor in slopes. Figure 2 graphically represents these findings in its middle part. Table 3. Piecewise mixed linear spline regression model with random effects on intercept and slopes predicting CRP and CRPlog2 in male and female neonates according to the timing of antibiotics start (at birth or after) and from antibiotics start to hour 30 after its start. Fixed effects CRP (mg/L) CRPlog2 (mg/L) Coefficient P-value [95% Conf. Interval] Coefficient P-value [95% Conf. Interval] Antibiotics started at birth ♂ Intercept (at antibiotic start) 4.495 <0.001 2.019 6.971 0.219 0.116 -0.054 0.492 ♀ 5.360 <0.001 2.461 8.259 0.279 0.088 -0.041 0.598 Delta ♀-♂ 0.866 0.656 -2.947 4.677 -0.060 0.78 -0.360 0.480 ♂ h0-12 slope (/h) 1.745 <0.001 1.403 2.086 0.317 <0.001 0.297 0.337 ♀ 1.744 <0.001 1.346 2.143 0.326 <0.001 0.303 0.350 Delta ♀-♂ -0.0004 0.999 -0.526 0.525 0.0093 0.560 -0.022 0.041 ♂ h12-30 slope (/h) 0.387 <0.001 0.230 0.544 0.033 <0.001 0.0257 0.041 ♀ 0.342 <0.001 0.156 0.527 0.027 <0.001 0.0182 0.036 Delta ♀-♂ -0.045 0.715 -0.288 0.197 -0.0061 0.309 -0.0179 0.0057 Antibiotics started after birth ♂ Intercept (at antibiotic start) 32.276 <0.001 30.716 33.836 4.900 <0.001 4.727 5.070 ♀ 33.273 <0.001 31.318 35.227 4.969 <0.001 4.754 5.184 Delta ♀-♂ 0.997 0.435 -1.504 3.497 0.071 0.616 -0.205 0.346 ♂ h0-12 slope (/h) 0.0252 0.816 -0.8176 0.238 -0.0041 0.531 -0.0168 0.0087 ♀ 0.270 0.049 0.0011 0.536 -0.0015 0.856 -0.0175 0.0145 Delta ♀-♂ 0.242 0.166 -0.101 0.584 0.0027 0.804 -0.0178 0.023 ♂ h12-30 slope (/h) -0.712 <0.001 -0.809 -0.614 -0.040 <0.001 -0.0447 -0.0351 ♀ -0.802 <0.001 -0.925 -0.680 -0.041 <0.001 -0.047 -0.035 Delta ♀-♂ -0.091 0.257 -0.248 0.066 -0.00157 0.687 -0.0092 0.0061 Number of patients 506 1525 506 1525 Number of observations Table 4 presents the various evolutions in CRP levels and its base 2 logarithm following CRP peak. At time 0 (CRP peak), both sexes had mean CRP values statistically different from 0 (32.65; 95% CI= 30.5 34.81 for males and 35.0; 95% CI 32.35 37.64 for females) with no statistically significant difference between sexes. In both sexes, CRP levels decreased (-0.32/hour; 95% CI= -0.34 -0.29 for males and -0.34/hour; 95% CI= -0.37 -0.31 for females) with no statistically significant difference between sexes. Figure 1 graphically represents these findings in its right part. Unfortunately, this model does not fit the data correctly as CRP would drop under zero after 96 hours from peak. The CRPlog2 model seems much more adequate in describing the CRP dropping kinetic. At time 0 (CRP peak), both sexes had mean CRPlog2 values statistically different from 0 (4.95; 95% CI= 4.87 5.04 for males and 5.04; 95% CI 4.94 5.15 for females) with no statistically significant difference between sexes. Therefore, we found no differences in CRP peak values between male and female neonates. In both sexes, CRPlog2 levels decreased (-0.032/hour; 95% CI= -0.033 -0.032 for males and -0.032/hour; 95% CI= -0.033 -0.031 for females) with no statistical difference between sexes. Thus, after the peak, CRP was reduced by half every 31.1 hours for males and 30.9 hours for females, with no statistically significant difference. Figure 2 represents graphically these findings in its right part. Discussion In our population, for every 2 female neonates, there were 3 male neonates included, reflecting a higher proportion of male neonates treated for EONS, consistent with figures reported by other authors [22]. The higher risk of jaundice in our male population can be attributed to the multiethnicity of the Brussels community, with a high prevalence of glucose-6-phosphate-dehydrogenase deficiency, a condition liked to a gene located on the X chromosome. Neonates in our population seem to present less likely preterm birth and low birth weight compared to current literature (median gestation age of 40 weeks versus 39 and birth weight of 3520 g versus 3250 g) [22]. The lower proportion of confirmed EONS compared to other authors (0% versus 375/21 703=1.7%) [22] can be explained by the characteristics of our NU, which serves as a peripheral non-referral center, with fewer preterm and critically ill neonates. CRP and CRPlog2 values in neonates with clinical NS significantly rise in the first 24 hours of life, showing a more significant rise than what is described in a healthy neonatal population [6]. Female neonates had an earlier and more rapid increase in CRP or CRPlog2 values with higher levels at 12 hours of life, consistent with what other authors have already described in children [14, 15]. Both sexes seem to reach a plateau of CRPlog2 at 24 hours of life, suggesting that male and female neonates would achieve the same level of CRPlog2 at a steady state, but female neonates would get there faster. The first hours of an inflammatory response mainly involve innate immunity, especially in neonates, whose adaptative immunity is still immature and depends significantly on the maternal antibodies providing only passive immunity against pathogens. This innate response is triggered by the detection of pathogen-associated molecular patterns by the Toll-like receptors (TLR) [23]. It leads to the production of pro-inflammatory cytokines, such as the IL-6, controlling the secretion of CRP by the hepatocytes. The genes of principal protein members of the TLR signaling pathway are linked to the X-chromosome [23], and polymorphisms of X-linked genes of the TLR pathway may play a role in the differences we observed. In the first 30 hours of antibiotics, we found no sex differences in CRP and CRPlog2 over time, likely due to the effect of the treatment initiated in clinical NS. On the other hand, we found a very different pattern between neonates treated at birth or after birth, especially in the first 12 hours after antibiotics start. Two non-contradictory hypotheses might explain these differences. In the first one, we assume that neonates treated at birth are more likely to be symptomatic and thus more critically ill, with a faster rise in CRP in the first 12 hours and a slower response to antibiotics failing to show a decrease in CRP levels between 12 and 30 hours after antibiotics start. This hypothesis is corroborated by the fact that neonates treated at birth had higher CRP and CRPlog2 values at birth compared to neonates treated after birth. In the second hypothesis, we assume that CRP may have an exponential pattern of growth until reaching a steady state. We could also assume that antibiotics have no effect on CRP levels in the first 12 hours of treatment. In this scenario of assumptions, the differences observed could be explained by the fact that antibiotics have been started after reaching the steady state for neonates treated after birth and before reaching the steady state for neonates treated at birth. The fact that the slope of the CRPlog2 in the first 12 hours of life before treatment is very similar to the slope of the first 12 hours of life of neonates treated at birth corroborates this hypothesis. It suggests that the logarithmic model is more adequate in describing the rising levels of CRP over time. We found no sex differences in the CRP decreasing phase. Our findings show how CRP clearly decreases following a logarithmic pattern with a considerably longer half-life (30-31 hours) compared to the 19 hours of adults [9]. Strength and limitations: To our knowledge, this is the first study describing sex-specific differences in inflammation in a population with clinical EONS. Moreover, previously described CRP values came from a primarily Caucasian healthy neonatal population [6]. Our study provides values from a multi-ethnic neonatal population with clinical EONS. Since prenatal infections are uncommon, we can assume with reasonable accuracy that birth (time zero) marks the beginning of the inflammation process. This timing is uncertain in other studies conducted on children or neonates with late-onset infections. This study has been conducted in a secondary center where preterm and critically ill neonates are poorly represented. Moreover, none of the cases had a microbiological confirmation, we cannot thus exclude the possibility that a lot of neonates with aseptic inflammation were included in the study population. Nevertheless, we could assume that CRP's ascending and descending pattern is likely to be the same regardless of the cause of inflammation. On the other hand, the aetiology of the inflammation certainly significantly influences the CRP evolution over time within the first 30 hours from the start of antibiotics. Accordingly, our results may primarily apply to a predominantly term neonatal population, with a small percentage of preterm neonates, in a secondary center with a multi-ethnic, high-income society. Moreover, the results concerning the first 30 hours of antibiotic treatment can only be extended to neonates with clinical EONS. Conclusion In neonates with clinical EONS, CRP probably increases following a logarithmic pattern. Before antibiotic treatment, female neonates in our population have a statistically significant earlier rise in CRP levels. On the other hand, we found no significant differences between sexes in CRP peak levels. After reaching its peak, CRP levels decreased following a logarithmic pattern with no differences between sexes. Abbreviations CRP: C-reactive protein; CRPlog2: base 2 logarithm of C-reactive protein; EIH: Etterbeek-Ixelles Hospital; EONS: early onset neonatal sepsis; IL: interleukin; LONS: late onset neonatal sepsis; MW: maternity ward; NS: neonatal sepsis; NU: neonatal unit; TLR: Toll-like receptors Declarations Ethics approval and consent to participate The study, with the reference CE/2024 – 01, was approved by the Etterbeek-Ixelles Hospital Ethics Committee which waived the need for an informed consent form. Consent for publication Not applicable. Clinical trial number Not applicable. Availability of data and materials The dataset analysed can be made available to interested researchers by the authors of this article. Competing interests The authors declare they have no competing interests. Funding The authors declare they received no funding. Authors contribution AN participated in study design and coordination, analysed the data, and drafted the manuscript. IE was responsible for data acquisition and coding and participated in manuscript writing. PCL NV GA NL AV participated in manuscript writing. All authors read and approved the final manuscript. Acknowledgements Not applicable References Shane AL, Sánchez PJ, Stoll BJ: Neonatal sepsis . Lancet 2017, 390 (10104):1770-1780. Wynn JL: Defining neonatal sepsis . Curr Opin Pediatr 2016, 28 (2):135-140. Sharma D, Farahbakhsh N, Shastri S, Sharma P: Biomarkers for diagnosis of neonatal sepsis: a literature review . J Matern Fetal Neonatal Med 2018, 31 (12):1646-1659. Benitz WE HM, Madan A, Ramachandra P. : Serial serum C-reactive protein levels in the diagnosis of neonatal infection. Pediatrics 1999, 102 . Eschborn S, Weitkamp JH: Procalcitonin versus C-reactive protein: review of kinetics and performance for diagnosis of neonatal sepsis . Journal of perinatology : official journal of the California Perinatal Association 2019, 39 (7):893-903. Chiesa C, Natale F, Pascone R, Osborn JF, Pacifico L, Bonci E, De Curtis M: C reactive protein and procalcitonin: reference intervals for preterm and term newborns during the early neonatal period . Clin Chim Acta 2011, 412 (11-12):1053-1059. Kaapa P, Koistinen E: Maternal and neonatal C-reactive protein after interventions during delivery . Artn Obstet Gynecol Scand 1993, 72 :543-546. Kawamura M, Nishida H: The usefulness of serial C-reactive protein measurement in managing neonatal infection . Acta Paediatr 1995, 84 :10-13. Vigushin DM PM, Hawkins PN.: Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health and disease. J Clin Invest 1993, 91 :1351-1357. van der Ende MY, Juarez-Orozco LE, Waardenburg I, Lipsic E, Schurer RAJ, van der Werf HW, Benjamin EJ, van Veldhuisen DJ, Snieder H, van der Harst P: Sex-Based Differences in Unrecognized Myocardial Infarction . J Am Heart Assoc 2020, 9 (13):e015519. Woodward M: Cardiovascular Disease and the Female Disadvantage . Int J Environ Res Public Health 2019, 16 (7). Watson RS, Carcillo JA, Linde-Zwirble WT, Clermont G, Lidicker J, Angus DC: The epidemiology of severe sepsis in children in the United States . Am J Respir Crit Care Med 2003, 167 (5):695-701. Ciesielski TH, Zhang X, Tacconelli A, Lutsar I, de Cabre VM, Roilides E, Ciccacci C, Borgiani P, Scott WK, Williams SM et al : Late-onset neonatal sepsis: genetic differences by sex and involvement of the NOTCH pathway . Pediatr Res 2023, 93 (4):1085-1095. Casimir GJ, Mulier S, Hanssens L, Zylberberg K, Duchateau J: Gender differences in inflammatory markers in children . Shock 2010, 33 (3):258-262. Lefevre N, Noyon B, Biarent D, Corazza F, Duchateau J, Casimir G: Sex Differences in Inflammatory Response and Acid-Base Balance in Prepubertal Children with Severe Sepsis . Shock 2017, 47 (4):422-428. Angele MK, Pratschke S, Hubbard WJ, Chaudry IH: Gender differences in sepsis: cardiovascular and immunological aspects . Virulence 2014, 5 (1):12-19. Schröder J, Kahlke V, Staubach KH, Zabel P, Stüber F: Gender differences in human sepsis . Arch Surg 1998, 133 (11):1200-1205. Kuzniewicz MW, Walsh EM, Li S, Fischer A, Escobar GJ: Development and Implementation of an Early-Onset Sepsis Calculator to Guide Antibiotic Management in Late Preterm and Term Neonates . Jt Comm J Qual Patient Saf 2016, 42 (5):232-239. Escobar GJ, Puopolo KM, Wi S, Turk BJ, Kuzniewicz MW, Walsh EM, Newman TB, Zupancic J, Lieberman E, Draper D: Stratification of risk of early-onset sepsis in newborns >/= 34 weeks' gestation . Pediatrics 2014, 133 (1):30-36. Puopolo KM, Draper D, Wi S, Newman TB, Zupancic J, Lieberman E, Smith M, Escobar GJ: Estimating the probability of neonatal early-onset infection on the basis of maternal risk factors . Pediatrics 2011, 128 (5):e1155-1163. Kuzniewicz MW, Puopolo KM, Fischer A, Walsh EM, Li S, Newman TB, Kipnis P, Escobar GJ: A Quantitative, Risk-Based Approach to the Management of Neonatal Early-Onset Sepsis . JAMA pediatrics 2017, 171 (4):365-371. Giannoni E, Dimopoulou V, Klingenberg C, Naver L, Nordberg V, Berardi A, El Helou S, Fusch G, Bliss JM, Lehnick D et al : Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia . JAMA Netw Open 2022, 5 (11):e2243691. Popotas A, Casimir GJ, Corazza F, Lefevre N: Sex-related immunity: could Toll-like receptors be the answer in acute inflammatory response? Front Immunol 2024, 15 :1379754. Additional Declarations No competing interests reported. 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Nebbioso","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEklEQVRIiWNgGAWjYHACAwgpwdgApGzgwjx8RGpJA2JmiBY2wlrA1GG4FgZcWvhnN2/78KHmjpy5dHPjwx8V5/PM2/sPPi7MsZNhY2B++OgGphaJO8eKZ8449szYcs7BZmOeM7eLZc4cZjaeuS0Z6DA2Y+McLNbcyDFm5mE7nLjhRmKbNGPb7cQZEsls0rzbgIJA70hj0SIP0vLn3+F6kBbJn23nYFrqcWoxAGlhbDucYADUIsHbdgCm5TBOLYY30ooZe/sOG+6E+CW5WILnsLEx77bjPGzM2P0idyN5M8OPb4flzaXbHwJDzC5Pgr3x4WPebdX2/OzNDx9j8z46SEAwmYlQjqZlFIyCUTAKRgEEAADuOGGPU8Y4pQAAAABJRU5ErkJggg==","orcid":"","institution":"Hôpital Etterbeek-Ixelles IRIS-sud","correspondingAuthor":true,"prefix":"","firstName":"Andrea","middleName":"","lastName":"Nebbioso","suffix":""},{"id":512517173,"identity":"23dbcff7-995e-4427-92e7-7d7d3841125d","order_by":1,"name":"Isaline Eggermont","email":"","orcid":"","institution":"Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B), Hôpital Universitaire des Enfants Reine Fabiola (HUDERF)","correspondingAuthor":false,"prefix":"","firstName":"Isaline","middleName":"","lastName":"Eggermont","suffix":""},{"id":512517174,"identity":"43f4b1d3-f23c-4da6-9064-5744fda207ca","order_by":2,"name":"Alfredo Vicinanza","email":"","orcid":"","institution":"Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B), Hôpital Universitaire des Enfants Reine Fabiola (HUDERF)","correspondingAuthor":false,"prefix":"","firstName":"Alfredo","middleName":"","lastName":"Vicinanza","suffix":""},{"id":512517175,"identity":"e75aa545-bf51-4701-8cc2-089edfff606b","order_by":3,"name":"Phu-Quoc Lê","email":"","orcid":"","institution":"Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B), Hôpital Universitaire des Enfants Reine Fabiola (HUDERF)","correspondingAuthor":false,"prefix":"","firstName":"Phu-Quoc","middleName":"","lastName":"Lê","suffix":""},{"id":512517176,"identity":"0b3d429c-34db-49cd-a64d-72834fcc0713","order_by":4,"name":"Nancy Vitali","email":"","orcid":"","institution":"Hôpital Etterbeek-Ixelles IRIS-sud","correspondingAuthor":false,"prefix":"","firstName":"Nancy","middleName":"","lastName":"Vitali","suffix":""},{"id":512517177,"identity":"7b743cc9-0ce0-4f14-aa39-1eea190b3b74","order_by":5,"name":"Gwenaëlle Augé","email":"","orcid":"","institution":"Hôpital Etterbeek-Ixelles IRIS-sud","correspondingAuthor":false,"prefix":"","firstName":"Gwenaëlle","middleName":"","lastName":"Augé","suffix":""},{"id":512517178,"identity":"cb565efe-cc8e-479c-b5cd-8252a2e1d4c2","order_by":6,"name":"Nicolas Lefèvre","email":"","orcid":"","institution":"Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B), Hôpital Universitaire des Enfants Reine Fabiola (HUDERF)","correspondingAuthor":false,"prefix":"","firstName":"Nicolas","middleName":"","lastName":"Lefèvre","suffix":""}],"badges":[],"createdAt":"2025-09-09 12:38:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7573907/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7573907/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91078216,"identity":"cfc1afdb-c11e-4dbe-9ead-012ee66c9126","added_by":"auto","created_at":"2025-09-11 11:19:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":211334,"visible":true,"origin":"","legend":"\u003cp\u003eGraphic representation of CRP concentrations according to regressions models shown in tables 2 (left part), 3 (middle part) and 4 (right part).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7573907/v1/3152343719526cff4c13398b.png"},{"id":91078217,"identity":"ff7d53eb-1cbd-43cf-b7dd-11f6238d20ea","added_by":"auto","created_at":"2025-09-11 11:19:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":220140,"visible":true,"origin":"","legend":"\u003cp\u003eGraphic representation of CRPlog2 according to regressions models shown in tables 2 (left part), 3 (middle part) and 4 (right part).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7573907/v1/125612744eb9fed1ed329775.png"},{"id":91082059,"identity":"9fbfaff5-7e21-4338-908d-a98f62b0f520","added_by":"auto","created_at":"2025-09-11 11:51:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2037613,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7573907/v1/7ba6a596-fb51-4b31-9692-403aa52c2211.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Mind the “CRP gender gap”! Sex differences in CRP evolution over time in neonatal sepsis: a monocentric retrospective cohort study","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eNeonatal sepsis (NS) has been defined as a systemic condition of infectious origin, resulting in substantial morbidity and mortality in neonates [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Most authors consider the first 72 hours of life the cut-off between early and late-onset NS, while others refer to late-onset NS (LONS) as occurring after seven days of life [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. When cultures are negative, but the infants manifest signs consistent with infection, they may be considered to have \u0026ldquo;clinical NS\u0026rdquo; [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. C-reactive protein (CRP) is the most widely used and readily available laboratory test to assess NS [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Two CRP values\u0026thinsp;\u0026lt;\u0026thinsp;10 mg/L obtained 24 hours apart have very high specificity and, therefore, strong power in excluding early onset NS (EONS) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]; however, once the clinician faces the opposite situation (one CRP measurement\u0026thinsp;\u0026gt;\u0026thinsp;10 mg/L), CRP cut-offs multiply and sensitivity drops below 70% [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Previous studies demonstrated that CRP values of healthy neonates are log-normally distributed and physiologically rise in the first 24 hours of life starting from a very low level at birth [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] as CRP does not pass through placenta [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. No sex differences in neonatal CRP levels have been found in a healthy neonatal population [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Many studies focused on the specificity and sensibility of CRP at specific times for the diagnosis of NS [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The evolution of CRP over time in neonates with NS or other inflammatory conditions has been poorly described. One study, with different primary goals, accidentally described CRP values over time in neonates with NS with few cases of confirmed NS, mostly in preterm, with only 4 cases of term neonates [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. No study has been published describing CRP values over time after antibiotic treatment in the neonatal population. The CRP decrease pattern over time after its initial peak has been described mainly in the adult population with an estimated half-life of 19 hours [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. We found no neonatal-specific data assessing CRP half-life after its peak. Increasing evidence suggest that overlooking sex differences in research leads to poorer outcomes for females [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. A large epidemiological study on severe sepsis in children in the United States confirmed that being male is a risk factor for worse outcomes in cases of prematurity and some neonatal infections [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Moreover, a genome-wide association study with 224 LONS cases showed that genetic susceptibility to LONS exhibits sexual dimorphism, with NOTCH signaling playing a role in determining the associated risk [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In children with sepsis or other infectious conditions, CRP values are more likely to be higher in females than males [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In the early stage of the infection, inflammatory biomarkers are more elevated in females, indicating a stronger immune activation. Over time, a distinct kinetic pattern emerges between sexes in the return to homeostasis. In contrast, levels of proinflammatory cytokines, such as interleukin (IL) 1β, IL-6, and tumor necrosis factor-alpha (TNF-α), are higher in men, whereas women exhibit elevated levels of anti-inflammatory mediators, notably IL-10 [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis study aims to determine whether there are sex-based differences in CRP kinetics over time during the early neonatal period in neonates with clinical NS. Our objective is to provide sex-based differential references describing how CRP rises before and stabilizes after antibiotic treatment and how quickly CRP decreases after its peak.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cb\u003eStudy design and setting.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis is a monocentric retrospective cohort study conducted in the neonatal unit (NU) and maternity ward (MW) of Etterbeek-Ixelles Hospital (EIH). We included all neonates born in the facility between January 2017 and December 2022 and treated with antibiotics. We excluded patients who started antibiotic therapy after 72 hours of life. Patients whose CRP concentrations remained under 10 mg/L during the hospital stay were also excluded. Only blood samples realized in EIH were considered in the analysis of patients who had to be transferred to other centers. EIH MW has an average of 2000 live births/year, and the NU has an admission rate of approximately 400 patients/year with a multi-ethnic patient population. Neonates treated with antibiotics in EIH MW are systematically admitted for the first few hours in the NU. As EIH NU provides sub-intensive neonatal care, preterm neonates before 32 weeks of gestational age are transferred to larger centers, as well as neonates with a birth weight under 1500 grams. EIH NU has incubators and can provide non-invasive ventilation, oxygen therapy, parenteral nutrition via central lines and nasogastric tube feeding. In EIH NU and MW, the first-line treatment of NS is a combination of amoxicillin-amikacin (5 days of amoxicillin and 2 days of amikacin), and the second-line treatment consists of the association of amoxicillin-cefotaxime. The tool of the neonatal sepsis risk calculator, as developed by Kuzniewicz et al., [\u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] has been systematically used to assess the NS risk since January 2020. In EIH NU and MW, CRP is measured before antibiotic treatment at 0, 12, and 24 hours of life in the presence of infectious risk factors. CRP is systematically measured 12 and 30 hours after antibiotic treatment.\u003c/p\u003e\u003cp\u003e\u003cb\u003eData Collection and statistical analysis\u003c/b\u003e.\u003c/p\u003e\u003cp\u003ePatients\u0026rsquo; files were retrospectively reviewed to collect the data. The following information was collected: date of birth, birth weight and its Z-score, gestational age at birth, sex, type of delivery, presence of risk factors for NS (meconial liquid, maternal fever, prolonged membrane rupture, maternal group B streptococcus colonization, chorioamnionitis and maternal antibiotic treatment), data about clinical presentation of neonates (fever, jaundice, respiratory distress, time of antibiotic start and blood culture result), CRP values and time of sampling. Frequencies and proportions were calculated for categorical variables. Fisher exact test was used to determine the association between categorical variables. Continuous variables were described using the median and interquartile range. Mann-Whitney test was performed for continuous variables. By convention, we decided to express time in hours and CRP in mg/L. We will refer to \u0026ldquo;base 2 CRP logarithm\u0026rdquo; (CRPlog2) as the base 2 logarithm of CRP values expressed in mg/L. We decided to describe CRP and CRPlog2 kinetic according to three different time axes. The first axis of time considers birth as time 0 and aims to describe the ascending phase of CRP and CRPlog2 before antibiotic start. The second axis of time considers antibiotic start as time 0 and seeks to describe the ascending-descending transition phase. The third axis of time designates time 0 as the point at which CRP peaks and aims to describe the subsequent descending phase. We fitted two identical models (one for CRP and one for CRPlog2) for each time axis. To describe the ascending kinetics of CRP and CRPlog2 for male and female neonates, we fitted a piecewise linear mixed-effects regression model where birth was considered as time zero with one knot at 12 hours of life, with observations occurring after 24 hours of life or after antibiotic treatment being excluded. Sex was the only covariate in this model. To describe the transition of CRP and CRPlog2 from ascending to descending phase, we fitted a piecewise linear mixed-effects regression model where antibiotic treatment start was considered as time zero with one knot at 12 hours of antibiotic treatment and observations occurring before antibiotic treatment or 30 hours after were excluded. Sex and time of antibiotic start (at birth vs after birth) were the two covariates in this model. To describe the descending kinetics of CRP and CRPlog2 for male and female neonates, we fitted a linear mixed-effects regression model where the CRP peak was considered as time zero, with observations occurring before the CRP peak or 120 hours after being excluded. Sex was the only covariate in this model. In all fitted models, we introduced a random effect on intercepts and slopes and we used the restricted maximum likelihood method to calculate standard error. We used an unstructured covariance matrix for serial correlation for all fitted models. A p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant. Statistical analyses were performed using STATA version 15.1 for MacOS (StataCorp, College Station, Texas 77845 USA).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the ethics committee of EIH MW (CE/2024 \u0026ndash; 01) and the reported investigations were carried out in accordance with the principles of the Declaration of Helsinki as revised in 2013.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the study period, 506 neonates met the inclusion criteria, with 304 males (60.1%) and 202 females (39.9%). Table 1 summarizes the population\u0026apos;s general demographic and clinical characteristics according to sex. In our population, 2.6% of neonates were born preterm, and 2.8% presented with a low birth weight. Treatment was started at birth in 29.4% of cases. Male neonates presented more frequently jaundice (12% vs 6.5%, p-value 0.047). We had no neonate with positive blood culture or fatal outcome.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e[Insert Table 1]\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2 shows the evolution of CRP and its base 2 logarithm before antibiotic treatment, in the first 12 hours of life and from 12 to 24 hours of life.\u003c/p\u003e\n\u003cp\u003eAt time 0 (birth) both sexes had mean CRP values statistically different from 0 (2.18; 95% CI= 1.41 2.94 for males and 2.34; 95% CI 1.41 3.27 for females) with no statistically significant difference between sexes. In both sexes CRP level rose in the first 12 hours of life (0.91/hour; 95% CI= 0.78 1.04 for males and 1.24/hour; 95% CI= 1.09 1.4 for females). Female neonates had a statistically significant faster rise in CRP (+ 0.34/hour; 95% CI= 0.13 0.54) compared to males. From hour 12 to hour 24 of life, CRP had a more rapid rise in both sexes (2.06/hour; 95% CI=1.92 2.21 for males and 1.91/hour; 95% CI= 1.72 2.1 for females) with no statistically significant difference between sexes. Figure 1 graphically represents these findings in its left part.\u003c/p\u003e\u003cp\u003eTable 1. General characteristics of neonates with CRP rise higher than 10 mg/L admitted to Ixelles neonatal unit (Bruxelles, Belgium) from January 2017 to December 2022.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"643\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003eMales (n=304)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003eFemales (n=202)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eTotal (n=506)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003eFisher\u0026rsquo;s exact/ Mann-Whitney test p-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNeonatal characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGestational age (n=506)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eLate preterm (32-37 weeks)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e10 (3.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e3 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e13 (2.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eTerm (\u0026gt;37 weeks)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e294 (96.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e199 (98.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e493 (97.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eGestational age weeks (median p25 p75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e40 (39 41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e40 (39 41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e40 (39 41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBirth weight (n=506)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eLow birth weight (1.5-2.5 kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e11 (3.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e3 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e14 (2.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eNormal birth weight (\u0026gt;2.5 kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e293 (96.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e199 (98.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e492 (97.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eBirth weight Kg (median p25 p75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e3.6 (3.23 3.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e3.43 (3.16 3.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e3.52 (3.2 3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eBirth weight Z-score (median p25 p75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0.10 (-0.48 0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e0.16 (-0.5 0.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e0.12 (-0.48 0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eRespiratory distress \u0026nbsp;(n=499)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e65 (21.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e44 (22.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e109 (21.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eJaundice (n=499)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e36 (12.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e13 (6.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e49 (9.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e0.047\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eFever (n=503)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e28 (9.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e19 (9.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e47 (9.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eTreatment started at birth (n=506)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e86 (28.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e63 (31.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e149 (29.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003ePositive blood culture (n=506)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eContaminant positive blood culture (n=506)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e7 (2.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e4 (2.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e11 (2.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 643px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDelivery characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDelivery type (n=506)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eVaginal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e141 (34.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e99 (49.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e240 (47.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eVacuum-assisted\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e106 (46.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e70 (34.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e176 (34.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eCaesar\u003cins cite=\"mailto:Andrea%20Nebbioso\" datetime=\"2024-12-18T22:26\"\u003ei\u003c/ins\u003ean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e57 (18.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e33 (16.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e90 (17.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInfectious risk factors\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eMaternal fever (n=491)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e56 (19.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e44 (22.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e100 (20.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eMaternal chorioamnionitis (n=500)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e8 (2.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e2 (1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e10 (2.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eProlonged membrane rupture (\u0026gt;18 h) (n=490)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e68 (23.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e38 (19.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e106 (21.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eMeconial amniotic liquid (n=476)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e113 (39.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e87 (45.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e200 (42.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eMaternal antibiotic treatment (n=499)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e154 (51.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e86 (43.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e240 (48.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 238px;\"\u003e\n \u003cp\u003eGBS colonisation (n=482)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e84 (29.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e42 (21.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e126 (26.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003e[Insert Figure 1]\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor CRPlog2 the pattern was quite similar with no statistically significant difference between sexes at birth and with both sexes having a mean CRPlog2 level different from 0 (-0.55; 95% CI=-0.75 -0.36 for males and -0.51; 95% CI= -0.75 -0.28 form females). In the first 12 hours, both sexes had a statistically significant rise in CRPlog2 (0.32/hour; 95% CI= 0.31 0.34 for males and 0.36/hour; 95% CI=0.34 0.38 for females) with a statistically significant faster rise of CRPlog2 in females (+0.037/hour 95% CI= 0.014 0.061). From hour 12 to hour 24 both sexes had a statistically significant rise in CRPlog2 (0.15/hour; 95% CI= 0.13 0.16 for males and 0.11/hour; 95% CI=0.09 0.13 for females) with a less rapid rise of CRPlog2 in females (-0.038/hour 95% CI= -0.064 -0.011). This means that, in our population, CRP plasma concentrations in the first 12 hours of life doubled every 3.1 hours for male neonates and every 2.8 hours for female neonates. Therefore, after the 12\u003csup\u003eth\u0026nbsp;\u003c/sup\u003ehour of life it took 6.8 hours for male neonates and 9.1 hours for female neonates, to double CRP plasma concentrations. Figure 2 graphically represents these findings in its left part.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e[Insert Figure 2]\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cimg 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\"\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 3 shows the different evolutions of CRP levels and its base 2 logarithm after antibiotic treatment, according to sex and the timing of antibiotic treatment (started at birth vs not); slopes are described in the first 12 hours of antibiotic treatment and afterward, up to 30 hours from antibiotic start.\u003c/p\u003e\n\u003cp\u003eFor neonates with antibiotics started at birth, at time 0 (antibiotic start and birth), both sexes had mean CRP values different from 0 (4.49; 95% CI= 2.02 6.47 for males and 5.36; 95% CI 2.46 8.26 for females). In both sexes, CRP levels rose in the first 12 hours of antibiotic treatment (1.74/hour; 95% CI= 1.4 2.09 for males and 1.74/hour; 95% CI= 1.35 2.14 for females). From hour 12 to hour 30 of antibiotic treatment, CRP kept rising at a less rapid rate in both sexes (0.39/hour; 95% CI= 0.23 0.54 for males and 0.34/hour; 95% CI= 0.16 0.53 for females). On the other hand, for neonates with antibiotics started after birth, at time 0 (antibiotic start), both sexes had mean CRP values statistically different from 0 (32.28; 95% CI= 30.72 33.84 for males and 33.27; 95% CI 31.32 35.23 for females), but these values were considerably higher than those of the neonates who received antibiotics at birth. Unlike neonates treated at birth, those treated after birth had CRP levels that remained stable in the first 12 hours of antibiotic treatment (0.025/hour; 95% CI= -0.82 0.24 for males and 0.27/hour; 95% CI= 0.001 0.54 for females) and from hour 12 to hour 30 of antibiotic treatment, CRP levels started to decrease (-0.71/hour; 95% CI= -0.81 -0.62 for males and -0.80/hour; 95% CI= -0.92 -0.68 for females). We found no statistically significant difference between sexes in both groups (antibiotics started at birth or after), neither in intercepts nor in slopes. Figure 1 graphically represents these findings in its middle part.\u003c/p\u003e\n\u003cp\u003eRegarding neonates with antibiotics started at birth, at time 0 (antibiotic start and birth), CRPlog2 values were not statistically different from 0 (0.22; 95% CI= -0.054 0.49 for males and 0.28; 95% CI -0.04 0.60 for females). In both sexes, CRPlog2 rose in the first 12 hours of antibiotic treatment (0.32/hour; 95% CI= 0.30 0.34 for males and 0.33/hour; 95% CI= 0.30 0.35 for females). From hour 12 to hour 30 of antibiotic treatment, CRPlog2 kept rising with a less rapid rate in both sexes (0.033/hour; 95% CI= 0.026 0.041 for males and 0.027/hour; 95% CI= 0.018 0.036 for females). On the other hand, for neonates with antibiotics started after birth, at time 0 (antibiotic start) both sexes had mean CRPlog2 values statistically different from 0 (4.9; 95% CI= 4.73 5.07 for males and 4.97; 95% CI 4.75 5.18 for females) and much higher compared to the neonates with antibiotics started at birth. Unlike neonates treated at birth, in those treated after birth, CRPlog2 remained stable in the first 12 hours of antibiotic treatment (-0.004/hour; 95% CI= -0.02 0.01 for males and -0.0015/hour; 95% CI= -0.02 0.014 for females) and from hour 12 to hour 30 of antibiotic treatment, CRPlog2 started to decrease (-0.04/hour; 95% CI= -0.045 -0.035 for males and -0.04/hour; 95% CI= -0.047 -0.035 for females). In both groups (antibiotic started at birth or after), we found no statistically significant difference between sexes, neither in intercept nor in slopes. Figure 2 graphically represents these findings in its middle part.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Table 3. Piecewise mixed linear spline regression model with random effects on intercept and slopes predicting CRP and CRPlog2 in male and female neonates according to the timing of antibiotics start (at birth or after) and from antibiotics start to hour 30 after its start.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"643\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 140px;\"\u003e\n \u003cp\u003eFixed effects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 249px;\"\u003e\n \u003cp\u003eCRP (mg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 253px;\"\u003e\n \u003cp\u003eCRPlog2 (mg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eCoefficient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 49px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 131px;\"\u003e\n \u003cp\u003e[95% Conf. Interval]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eCoefficient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 132px;\"\u003e\n \u003cp\u003e[95% Conf. Interval]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 140px;\"\u003e\n \u003cp\u003eAntibiotics started at birth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e♂\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 67px;\"\u003e\n \u003cp\u003eIntercept\u003c/p\u003e\n \u003cp\u003e(at antibiotic start)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e4.495\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e2.019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e6.971\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.219\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e0.116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e-0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.492\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e♀\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e5.360\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e2.461\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e8.259\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.279\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e0.088\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e-0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.598\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eDelta\u0026nbsp;♀-♂\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e0.866\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.656\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e-2.947\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e4.677\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e-0.060\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e-0.360\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.480\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e♂\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 67px;\"\u003e\n \u003cp\u003eh0-12\u003c/p\u003e\n \u003cp\u003eslope\u003c/p\u003e\n \u003cp\u003e(/h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e1.745\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.403\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e2.086\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.317\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e0.297\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.337\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e♀\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e1.744\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.346\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e2.143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.326\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e0.303\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.350\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eDelta\u0026nbsp;♀-♂\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e-0.0004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e-0.526\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.525\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.0093\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e0.560\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e-0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e♂\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 67px;\"\u003e\n \u003cp\u003eh12-30\u003c/p\u003e\n \u003cp\u003eslope\u003c/p\u003e\n \u003cp\u003e(/h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e0.387\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e0.230\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.544\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e0.0257\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e♀\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e0.342\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e0.156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.527\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.027\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e0.0182\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eDelta ♀-♂\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e-0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.715\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e-0.288\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.197\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e-0.0061\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e0.309\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e-0.0179\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.0057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 140px;\"\u003e\n \u003cp\u003eAntibiotics started after birth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e♂\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 67px;\"\u003e\n \u003cp\u003eIntercept\u003c/p\u003e\n \u003cp\u003e(at antibiotic start)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e32.276\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e30.716\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e33.836\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e4.900\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e4.727\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e5.070\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e♀\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e33.273\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e31.318\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e35.227\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e4.969\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e4.754\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e5.184\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eDelta\u0026nbsp;♀-♂\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e0.997\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.435\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e-1.504\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e3.497\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.071\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e0.616\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e-0.205\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.346\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e♂\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 67px;\"\u003e\n \u003cp\u003eh0-12\u003c/p\u003e\n \u003cp\u003eslope\u003c/p\u003e\n \u003cp\u003e(/h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e0.0252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.816\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e-0.8176\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.238\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e-0.0041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e0.531\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e-0.0168\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.0087\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e♀\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e0.270\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.049\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e0.0011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.536\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e-0.0015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e0.856\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e-0.0175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.0145\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eDelta ♀-♂\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e0.242\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.166\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e-0.101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.584\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.0027\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e0.804\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e-0.0178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e♂\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 67px;\"\u003e\n \u003cp\u003eh12-30\u003c/p\u003e\n \u003cp\u003eslope\u003c/p\u003e\n \u003cp\u003e(/h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e-0.712\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e-0.809\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e-0.614\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e-0.040\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e-0.0447\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e-0.0351\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e♀\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e-0.802\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e-0.925\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e-0.680\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e-0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e-0.047\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e-0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003eDelta ♀-♂\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e-0.091\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.257\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e-0.248\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.066\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e-0.00157\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e0.687\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e-0.0092\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.0061\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 140px;\"\u003e\n \u003cp\u003eNumber of patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" rowspan=\"2\" style=\"width: 249px;\"\u003e\n \u003cp\u003e506\u003c/p\u003e\n \u003cp\u003e1525\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" rowspan=\"2\" style=\"width: 253px;\"\u003e\n \u003cp\u003e506\u003c/p\u003e\n \u003cp\u003e1525\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 140px;\"\u003e\n \u003cp\u003eNumber of observations\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTable 4 presents the various evolutions in CRP levels and its base 2 logarithm following CRP peak. At time 0 (CRP peak), both sexes had mean CRP values statistically different from 0 (32.65; 95% CI= 30.5 34.81 for males and 35.0; 95% CI 32.35 37.64 for females) with no statistically significant difference between sexes. In both sexes, CRP levels decreased (-0.32/hour; 95% CI= -0.34 -0.29 for males and -0.34/hour; 95% CI= -0.37 -0.31 for females) with no statistically significant difference between sexes. Figure 1 graphically represents these findings in its right part. Unfortunately, this model does not fit the data correctly as CRP would drop under zero after 96 hours from peak.\u003c/p\u003e\n\u003cp\u003eThe CRPlog2 model seems much more adequate in describing the CRP dropping kinetic. At time 0 (CRP peak), both sexes had mean CRPlog2 values statistically different from 0 (4.95; 95% CI= 4.87 5.04 for males and 5.04; 95% CI 4.94 5.15 for females) with no statistically significant difference between sexes. Therefore, we found no differences in CRP peak values between male and female neonates. In both sexes, CRPlog2 levels decreased (-0.032/hour; 95% CI= -0.033 -0.032 for males and -0.032/hour; 95% CI= -0.033 -0.031 for females) with no statistical difference between sexes. Thus, after the peak, CRP was reduced by half every 31.1 hours for males and 30.9 hours for females, with no statistically significant difference. Figure 2 represents graphically these findings in its right part.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cimg 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\"\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our population, for every 2 female neonates, there were 3 male neonates included, reflecting a higher proportion of male neonates treated for EONS, consistent with figures reported by other authors [22]. The higher risk of jaundice in our male population can be attributed to the multiethnicity of the Brussels community, with a high prevalence of glucose-6-phosphate-dehydrogenase deficiency, a condition liked to a gene located on the X chromosome. Neonates in our population seem to present less likely preterm birth and low birth weight compared to current literature (median gestation age of 40 weeks versus 39 and birth weight of 3520 g versus 3250 g) [22]. The lower proportion of confirmed EONS compared to other authors (0% versus 375/21 703=1.7%) [22] can be explained by the characteristics of our NU, which serves as a \u0026nbsp;peripheral non-referral center, with fewer preterm and critically ill neonates. CRP and CRPlog2 values in neonates with clinical NS significantly rise in the first 24 hours of life, showing a more significant rise than what is described in a healthy neonatal population [6]. Female neonates had an earlier and more rapid increase in CRP or CRPlog2 values with higher levels at 12 hours of life, consistent with what other authors have already described in children [14, 15]. Both sexes seem to reach a plateau of CRPlog2 at 24 hours of life, suggesting that male and female neonates would achieve the same level of CRPlog2 at a steady state, but female neonates would get there faster. The first hours of an inflammatory response mainly involve innate immunity, especially in neonates, whose adaptative immunity is still immature and depends significantly on the maternal antibodies providing only passive immunity against pathogens. This innate response is triggered by the detection of pathogen-associated molecular patterns by the Toll-like receptors (TLR) [23]. It leads to the production of pro-inflammatory cytokines, such as the IL-6, controlling the secretion of CRP by the hepatocytes. The genes of principal protein members of the TLR signaling pathway are linked to the X-chromosome [23], and polymorphisms of X-linked genes of the TLR pathway may play a role in the differences we observed. In the first 30 hours of antibiotics, we found no sex differences in CRP and CRPlog2 over time, likely due to the effect of the treatment initiated in clinical NS. On the other hand, we found a very different pattern between neonates treated at birth or after birth, especially in the first 12 hours after antibiotics start. Two non-contradictory hypotheses might explain these differences. In the first one, we assume that neonates treated at birth are more likely to be symptomatic and thus more critically ill, with a faster rise in CRP in the first 12 hours and a slower response to antibiotics failing to show a decrease in CRP levels between 12 and 30 hours after antibiotics start. This hypothesis is corroborated by the fact that neonates treated at birth had higher CRP and CRPlog2 values at birth compared to neonates treated after birth. In the second hypothesis, we assume that CRP may have an exponential pattern of growth until reaching a steady state. We could also assume that antibiotics have no effect on CRP levels in the first 12 hours of treatment. In this scenario of assumptions, the differences observed could be explained by the fact that antibiotics have been started after reaching the steady state for neonates treated after birth and before reaching the steady state for neonates treated at birth. The fact that the slope of the CRPlog2 in the first 12 hours of life before treatment is very similar to the slope of the first 12 hours of life of neonates treated at birth corroborates this hypothesis. It suggests that the logarithmic model is more adequate in describing the rising levels of CRP over time. We found no sex differences in the CRP decreasing phase. Our findings show how CRP clearly decreases following a logarithmic pattern with a considerably longer half-life (30-31 hours) compared to the 19 hours of adults [9]. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStrength and limitations:\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo our knowledge, this is the first study describing sex-specific differences in inflammation in a population with clinical EONS. Moreover, previously described CRP values came from a primarily Caucasian healthy neonatal population [6]. Our study provides values from a multi-ethnic neonatal population with clinical EONS. Since prenatal infections are uncommon, we can assume with reasonable accuracy that birth (time zero) marks the beginning of the inflammation process. This timing is uncertain in other studies conducted on children or neonates with late-onset infections. This study has been conducted in a secondary center where preterm and critically ill neonates are poorly represented. Moreover, none of the cases had a microbiological confirmation, we cannot thus exclude the possibility that a lot of neonates with aseptic inflammation were included in the study population. Nevertheless, we could assume that CRP\u0026apos;s ascending and descending pattern is likely to be the same regardless of the cause of inflammation. On the other hand, the aetiology of the inflammation certainly significantly influences the CRP evolution over time within the first 30 hours from the start of antibiotics. Accordingly, our results may primarily apply to a predominantly term neonatal population, with a small percentage of preterm neonates, in a secondary center with a multi-ethnic, high-income society. Moreover, the results concerning the first 30 hours of antibiotic treatment can only be extended to neonates with clinical EONS. \u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn neonates with clinical EONS, CRP probably increases following a logarithmic pattern. Before antibiotic treatment, female neonates in our population have a statistically significant earlier rise in CRP levels. On the other hand, we found no significant differences between sexes in CRP peak levels. After reaching its peak, CRP levels decreased following a logarithmic pattern with no differences between sexes.\u0026nbsp;\u003c/p\u003e\n"},{"header":"Abbreviations","content":"\u003cp\u003eCRP: C-reactive protein; CRPlog2: base 2 logarithm of C-reactive protein; EIH: Etterbeek-Ixelles Hospital; EONS: early onset neonatal sepsis; IL: interleukin; LONS: late onset neonatal sepsis; MW: maternity ward; NS: neonatal sepsis; NU: neonatal unit; TLR: Toll-like receptors\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study, with the reference CE/2024 \u0026ndash; 01, was approved by the Etterbeek-Ixelles Hospital Ethics Committee which waived the need for an informed consent form.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe dataset analysed can be made available to interested researchers by the authors of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare they received no funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAN participated in study design and coordination, analysed the data, and drafted the manuscript. IE was responsible for data acquisition and coding and participated in manuscript writing. PCL NV GA NL AV participated in manuscript writing. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eShane AL, S\u0026aacute;nchez PJ, Stoll BJ: \u003cstrong\u003eNeonatal sepsis\u003c/strong\u003e. \u003cem\u003eLancet \u003c/em\u003e2017, \u003cstrong\u003e390\u003c/strong\u003e(10104):1770-1780.\u003c/li\u003e\n\u003cli\u003eWynn JL: \u003cstrong\u003eDefining neonatal sepsis\u003c/strong\u003e. \u003cem\u003eCurr Opin Pediatr \u003c/em\u003e2016, \u003cstrong\u003e28\u003c/strong\u003e(2):135-140.\u003c/li\u003e\n\u003cli\u003eSharma D, Farahbakhsh N, Shastri S, Sharma P: \u003cstrong\u003eBiomarkers for diagnosis of neonatal sepsis: a literature review\u003c/strong\u003e. \u003cem\u003eJ Matern Fetal Neonatal Med \u003c/em\u003e2018, \u003cstrong\u003e31\u003c/strong\u003e(12):1646-1659.\u003c/li\u003e\n\u003cli\u003eBenitz WE 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El Helou S, Fusch G, Bliss JM, Lehnick D\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eAnalysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia\u003c/strong\u003e. \u003cem\u003eJAMA Netw Open \u003c/em\u003e2022, \u003cstrong\u003e5\u003c/strong\u003e(11):e2243691.\u003c/li\u003e\n\u003cli\u003ePopotas A, Casimir GJ, Corazza F, Lefevre N: \u003cstrong\u003eSex-related immunity: could Toll-like receptors be the answer in acute inflammatory response?\u003c/strong\u003e \u003cem\u003eFront Immunol \u003c/em\u003e2024, \u003cstrong\u003e15\u003c/strong\u003e:1379754.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"CRP, neonatal sepsis, neonatal infection, neonatal inflammation, inflammation, sex differences, sexual dimorphism","lastPublishedDoi":"10.21203/rs.3.rs-7573907/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7573907/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eC-reactive protein (CRP) is a readily available test widely used to assess neonatal sepsis (NS). In children with sepsis or other infectious conditions, CRP is more likely to be higher in females than males, however, evidence is lacking on sex differences in CRP in the neonatal population. This study aims to describe sex differences of CRP evolution in the ascending and decreasing phase after its peak in neonates with clinical NS.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis is a monocentric retrospective cohort study conducted at Etterbeek-Ixelles Hospital in Brussels. We included all neonates born in the facility between January 2017 and December 2022 who received antibiotics in the first 72 hours of life. Patients whose CRP concentrations remained under 10 mg/L were excluded. To describe the ascending kinetics of CRP and its logarithm for male and female neonates, we fitted a piecewise linear mixed-effects regression model with birth considered as time zero and one knot at 12 hours of life. We used a linear mixed-effects regression model with CRP peak considered as time zero to describe CRP's descending kinetics and its logarithm for male and female neonates.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eWe included 506 neonates (60.1% male and 39.9% female). CRP concentration in the first 12 hours of life doubled every 3.1 and 2.8 hours, respectively, in males and females, with female neonates having a statistically significant faster rise of base 2 logarithm of CRP (+\u0026thinsp;0.037/hour 95% CI\u0026thinsp;=\u0026thinsp;+\u0026thinsp;0.014\u0026thinsp;+\u0026thinsp;0.061). After 12 hours of life, CRP doubled every 6.8 and 9.1 hours, respectively, in males and females, with female neonates having a statistically significant slower rise of base 2 logarithm of CRP (-0.038/hour 95% CI= -0.011 -0.064). After its peak, CRP decreased by half every 31.1 and 30.9 hours, respectively, for males and females.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eIn neonates of both sexes with clinical early-onset NS, CRP seems to increase, reach a peak, and then decrease, following a logarithmic pattern. Before antibiotic treatment, female neonates in our population had a statistically significant earlier increase in CRP levels, with no significant difference in the peak levels of CRP.\u003c/p\u003e","manuscriptTitle":"Mind the “CRP gender gap”! Sex differences in CRP evolution over time in neonatal sepsis: a monocentric retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-11 11:18:59","doi":"10.21203/rs.3.rs-7573907/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"739cf7f2-848f-4519-8f61-0bde7c08d6cf","owner":[],"postedDate":"September 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-17T03:38:37+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-11 11:18:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7573907","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7573907","identity":"rs-7573907","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}