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Keywords:

  • subfebrile maternal temperature;
  • neonatal seizures;
  • asphyxia;
  • sepsis;
  • perinatal outcomes

Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Statistical analysis
  5. Results
  6. Comment
  7. References
  8. Supporting Information

Background

Subfebrile intrapartum maternal temperature is very common, yet there is sparse evidence regarding its causes or its effects on perinatal outcomes. We examined whether mild temperature elevation during labour is a risk marker for adverse obstetric and neonatal outcomes.

Methods

A retrospective cohort analysis including 42 601 term, singleton live-births in two medical centres between 2003 and 2010 was performed. This study compared women who experienced a maximal intrapartum temperature of ≤37°C with women who experienced subfebrile intrapartum temperature (37.1–37.9°C). Adjusted risks for adverse obstetric and neonatal outcomes were calculated by using multivariable logistic regression models.

Results

Compared with maternal temperature ≤ 37°C, subfebrile temperature was associated with higher rates of primary caesarean deliveries {adjusted odds ratios [aOR] = 1.36 [95% confidence interval (CI) 1.25, 1.49])} and assisted vaginal deliveries (aOR = 1.20 [95% CI 1.11, 1.30]), as well as with greater risks of early neonatal sepsis (aOR = 2.66 [95% CI 1.88, 3.77]), neonatal intensive care unit admissions (aOR = 1.40 [95% CI 1.08, 1.83]), and neonatal asphyxia or seizures (aOR = 3.18 [95% CI 1.51, 6.70]). Mildly elevated maternal intrapartum temperature (37.1–37.5°C) was also associated with adverse outcomes.

Conclusions

Maternal intrapartum subfebrile temperature may be an indicator of operative delivery and neonatal morbidity. Further research is needed to confirm these findings and to reveal underlying mechanisms.

Body temperature is controlled by the thermoregulatory centre, which is located in the anterior hypothalamus. The body is normally able to maintain a fairly steady temperature because the hypothalamic thermoregulatory centre balances excess heat production, derived from metabolic activity in muscles and the liver with heat dissipation from the skin and lungs. When fever occurs, the hypothalamic set-point shifts upwards into febrile levels as a result of prostaglandin E2 (PGE2) elevation, which activates neurons in the vasomotor centre to commence vasoconstriction and warm-sensing neurons to slow their firing rate and increase heat production in the periphery.[1]

Intrapartum fever is a well-known risk factor for adverse neonatal outcomes, including transient adverse effects on the newborn, such as the need for respiratory support,[2] as well as neonatal morbidity (infection, meconium aspiration, and seizures) and mortality.[3] Intrapartum fever is also associated with adverse obstetric outcomes, such as postpartum haemorrhage, labour dystocia,[4] caesarean delivery, and assisted vaginal delivery.[5]

Intrapartum fever, usually defined as a temperature ≥ 38°C, might be a result of maternal or fetal infection,[6] particularly chorioamnionitis;[7] an increased metabolic rate;[8] or the use of epidural analgesia.[6, 9] Some investigators suggest that in the vast majority of patients, the aetiology for intrapartum fever is non-infectious, particularly when resulting from epidural analgesia.[10]

In clinical practice, a body temperature that is slightly above normal but not febrile is referred to as a subfebrile temperature. To date, there is little evidence regarding the association of subfebrile body temperature during labour with obstetric and neonatal outcomes. This study aimed to determine whether the development of subfebrile temperature during labour is a risk marker for obstetric and neonatal complications.

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Statistical analysis
  5. Results
  6. Comment
  7. References
  8. Supporting Information

We conducted a historical cohort of all singleton livebirths that took place on two campuses of a tertiary medical centre in Jerusalem, Israel, between 1 January 2003 and 16 January 2011. This centre is comprised of two medical centres that serve as both community and tertiary (referral) centres and that during the study period took care of approximately 40% of the deliveries of the Jerusalem population. These public hospitals are accessible to all women without any cost. Our cohort included parturients younger than 50 years who gave birth at term (i.e. ≥37 weeks gestation) to neonates weighing up to 5000 grams and who spent at least 1 h in the delivery room. We excluded elective and semi-elective caesarean deliveries (caesarean deliveries indicated before entering the delivery room, e.g. breech presentation in labour, parturients after two caesarean sections arriving to the triage in labour), trials of labour after a previous caesarean delivery (because of association with higher rates of adverse obstetrical outcomes and operative deliveries), use of prostaglandins during induction of labour (because of their effect on body temperature elevation), fetal malformations, chromosomal abnormalities, unknown temperature during labour, and parturients who experienced intrapartum fever (≥38°C).

Data were retrieved from the electronic logbook of the delivery room. Clinical characteristics that were collected and analysed included maternal age, parity, gestational age at delivery, birthweight, use of epidural analgesia, length of labour reflecting the length of phase 1 and 2 of labour, and maternal maximal oral temperature during labour that is correlated with intrauterine temperature during labour.[11] We routinely measure parturients temperature before entering the delivery room. After admission to the delivery room, temperature measurement is repeated once in 8 h. Measurement of temperature is repeated again during the next hour if a reading is febrile (≥38°C). Additionally, temperature measurement is repeated if there are clinical signs of temperature elevation (e.g. maternal or fetal tachycardia, maternal shivering, sweating, or a subjective sensation of fever). The study population was divided according to the maximal temperature measured during labour as follows: non-febrile parturients (NFP) who experienced a maximal temperature of ≤ 37°C and subfebrile parturients (SFP) who experienced a maximal temperature of 37.1–37.9°C. SFP were further divided into two groups: low subfebrile parturients (LSFP) who experienced a maximal temperature of 37.1–37.5°C and high subfebrile parturients (HSFP) who experienced a maximal temperature of 37.6–37.9°C.

The study's main obstetric outcomes were rates of caesarean deliveries and assisted vaginal deliveries, namely vacuum extractions because almost all (98%) assisted vaginal deliveries in our delivery room were performed by vacuum. The main neonatal outcomes were low Apgar score at 1 (≤4) and 5 min (≤7); neonatal intensive care unit (NICU) admissions; and neonatal morbidities, including seizures until discharge, asphyxia, and early-onset sepsis. Criteria for NICU admission of term neonates includes symptomatic neonates that needs further observation and treatment. Asymptomatic term infants, including those requiring sepsis work-up and observation because of maternal complications during labour, are not admitted to the NICU and are followed in the general nursery by a neonatologist. Birth asphyxia related to hypoxic ischaemic encephalopathy was defined if the infant's Apgar score at 10 min after birth was ≤5 or if there was a continued need for resuscitation, with acidosis (defined as any occurrence of umbilical cord, arterial, or capillary pH of <7.00 or base deficit of ≥16 mmol/L). Additional criteria were moderate-to-severe encephalopathy (indicated by lethargy, stupor, or coma) and one of the following: hypotonia, abnormal reflexes, an absent or weak suck, or clinical seizures. Seizures were clinically observed by at least one trained neonatologist. In each case, electroencephalography was performed to confirm abnormal background activity, asymmetry or seizure activity.[12]

Early-onset sepsis was defined as a blood culture with or without a cerebrospinal fluid culture that was positive for a bacterial species and was obtained from an infant under 72 h of age.[13] If blood cultures taken during these 72 h of life were positive for bacterial growth and cerebrospinal fluid cultures were not obtained immediately after birth, a lumbar puncture was performed after the confirmation of bacterial growth in the blood. Blood cultures evaluation included discrimination of blood culture contaminations mainly by coagulase-negative Staphylococcus. Contamination vs. true infection was confirmed after confirming that a repeated blood culture, before the commencement of antibiotic, was sterile.

Statistical analysis

  1. Top of page
  2. Abstract
  3. Methods
  4. Statistical analysis
  5. Results
  6. Comment
  7. References
  8. Supporting Information

To compare the study covariates between parturients by intrapartum temperature groups, we first used the chi-square and t-test, as appropriate. Unadjusted and adjusted odds ratios (aOR) for adverse obstetric and neonatal outcomes were calculated using univariate and multivariable logistic regression models. Obstetric outcomes models controlled for maternal age (continuous), parity (dichotomous: nulliparous/ multiparous), gestational age (categorical: 37–39, 40–41, ≥42), labour length (continuous), and epidural analgesia (yes/no). Neonatal outcomes models controlled for gestational age, birth weight, grams (categorised: <2500, 2500–4000, >4000), labour length, and epidural analgesia. To adjust for residual confounding, a subanalysis divided to nulliparous and multiparous parturients was carried out. The statistical software package SPSS 20.0 (SPSS Inc., Chicago, IL, USA) was used for all data analyses. We report odds ratios (OR), 95% confidence interval [CI], and two-sided P-values. The study protocol was approved by the Institutional Review Board.

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Statistical analysis
  5. Results
  6. Comment
  7. References
  8. Supporting Information

Among 42 601 births included in the study during the 7-year research period, 31 053 parturients (72.9%) had a maximal temperature during labour of ≤37.0°C (NFP) and 11 548 parturients (27.1%) had subfebrile temperature (i.e. a maximal temperature during labour of 37.1–37.9°C) (SFP). The clinical characteristics of the study population are presented in Table 1. SFP were more likely than NFP to be nulliparous (47.3% vs. 31.4%, P < 0.001). Compared with NFP, SFP had higher rates of labour induction and use of epidural analgesia during labour (22.7% vs. 12.1% and 71.5% vs. 59.7%, respectively, P < 0.001). The mean labour length was longer in the SFP group.

Table 1. Characteristics of parturients by intrapartum temperature
CharacteristicNFP (N = 31 053)SFP (N = 11 548)P-value
N%N%
  1. NFP, non-febrile parturients; SFP, subfebrile parturients; NS, not significant; SD, standard deviation.

Maternal age<205211.71481.3<0.001
20–3424 98380.5955982.8
35–44548017.6182415.8
≥45690.2170.1
Parity1975231.4545847.3<0.001
2–518 76260.4513344.4
6+25398.29578.3
Gestational week37–3914 67647.3535246.3
40–4115 40049.6570049.4
≥429773.14964.3
Birth weight (grams)<25006402.12902.5<0.001
2500–349920 26365.3745464.5
3500–3999835926.9312427.1
≥400017915.86805.9
Labour characteristicsEpidural18 52459.7826271.5<0.0001
Induction of labour377212.1262522.7<0.0001
Phase 2 (min) [mean, (SD)]38.2 (50.1)59.1 (64.7)<0.001
Phase 3 (min) [mean, (SD)]10.9 (25.5)11.3 (17.9)NS
Labour length (h) [mean, (SD)]5.9 (6.0)9.5 (8.2)<0.001

Unadjusted and adjusted OR of obstetric and neonatal outcomes of SFP is presented in Table 2. After controlling for potential confounders, the odds for primary caesarean section and assisted vaginal delivery were higher in the SFP group as compared with the NFP group (aOR = 1.36 [95% CI 1.25, 1.49] and aOR = 1.20 [95% CI 1.11, 1.30], respectively). Also, neonatal outcomes were worse in the SFP group. After adjustment, the odds for low Apgar score, NICU admissions, and neonatal morbidity (including neonatal asphyxia, seizures, and sepsis) were higher in the SFP group as compared with the NFP group. In particular, the OR for early neonatal sepsis was 2.66 [95% CI 1.88, 3.77].

Table 2. Obstetric and neonatal outcomes of parturients with intrapartum subfebrile temperature
   Univariable modelMultivariable modelb
OutcomeNFPa (N = 31 053)SFPa (N = 11 548)ORc95% CIaORc95% CI
  1. a

    Presented in %.

  2. b

    Primary C/S and assisted vaginal delivery models adjusted for: age, parity, gestational age (weeks), epidural and labour length; Apgar scores, NICU admissions, neonatal asphyxia or convulsions and neonatal sepsis models adjusted for: Epidural, birth weight, gestational age (weeks) and labour length.

  3. c

    Odds of event for SFP/Odds of event for NFP.

  4. d

    Data missing for 139 and 36 cases of NFP and SFP, respectively.

  5. NFP, non-febrile parturients; SFP, subfebrile parturients; OR, odds ratio; aOR, adjusted odds ratio; CI, confidence interval; NICU, neonatal intensive care unit.

Primary caesarean5.09.72.05[1.90, 2.23]1.36[1.25, 1.49]
Assisted vaginal delivery6.611.11.76[1.63, 1.90]1.20[1.11, 1.30]
Apgar 1 min ≤4d0.20.42.14[1.46, 3.15]2.03[1.38, 2.99]
Apgar 5 min ≤7d0.20.31.68[1.12, 2.51]1.61[1.07, 2.42]
NICU admission0.50.81.52[1.18, 1.97]1.40[1.08, 1.83]
Neonatal asphyxia or seizures0.10.13.81[1.82, 7.99]3.18[1.51, 6.70]
Neonatal sepsis0.20.62.87[2.03, 4.05]2.66[1.88, 3.77]

In the SFP group, 10 175 parturients (88.1%) experienced a maximal temperature of 37.1–37.5°C (LSFP), and 1373 parturients (11.9%) experienced a maximal temperature of 37.6–37.9°C (HSFP). When examining the relationship between intrapartum subfebrile temperature and rates of adverse obstetric and neonatal outcomes among LSFP and HSFP groups, there was a dose–response effect in the cases of primary caesarean deliveries, assisted vaginal deliveries, and early neonatal sepsis (Figure 1). Unadjusted and adjusted ORs of obstetric and neonatal outcomes of LSFP and HSFP are presented in Table 3. As compared with the NFP group, the aOR for primary caesarean deliveries was 1.26 [95% CI 1.15, 1.38] among LSFP and 2.01 [95% CI 1.72, 2.36] among HSFP. Among LSFP, the aOR for low Apgar scores at 1 and 5 min were 2.06 [95% CI 1.38, 3.07] and 1.64 [95% CI 1.07, 2.50], respectively. The risk for NICU admissions was also higher for the LSFP (aOR = 1.48 [95% CI 1.13, 1.93]). The aOR for neonatal asphyxia and seizures was 3.49 [95% CI 1.64, 7.39] among LSFP. Because there was only one case of asphyxia and seizure in the HSFP group, ORs were not calculated. The aOR for early neonatal sepsis was 2.45 [95% CI 1.70, 3.54] among LSFP and 4.24 [95% CI 2.31, 7.80] among HSFP. Interestingly, no significant associations were demonstrated between intrapartum maternal temperature of 37.6–37.9 (HSFP) and low Apgar scores and NICU admissions.

figure

Figure 1. (a) Rates of operative delivery by degree of maternal intrapartum temperature. Rates of caesarean sections and assisted vaginal deliveries are presented by three subgroups of maternal intrapartum temperature: non-febrile parturients (NFP, ≤37.0°C), low subfebrile parturients (LSFP, 37.1–37.5°C), and high subfebrile parturients (HSFP, 37.6–37.9°C). (b) Rates of adverse neonatal outcomes by degree of maternal intrapartum temperature. Rates of neonatal intensive care unit (NICU) admissions, neonatal asphyxia, and seizures and early neonatal sepsis are presented by three subgroups of maternal intrapartum temperature: non-febrile parturients (NFP, ≤37.0°C), low subfebrile parturients (LSFP, 37.1–37.5°C), and high subfebrile parturients (HSFP, 37.6–37.9°C).

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Table 3. Obstetric and neonatal outcomes of parturients with low and high intrapartum sub–febrile temperature
 LSFP (N = 10 175)HSFP (N = 1373)
Univariable modelMultivariable modelaUnivariable modelMultivariable modela
OutcomeORb95% CIaORb95% CIORb95% CIaORb95% CI
  1. a

    Primary C/S and assisted vaginal delivery models adjusted for: age, parity, gestational age (weeks), epidural and labour length; Apgar scores, NICU admissions, neonatal asphyxia or convulsions and neonatal sepsis models adjusted for: Epidural, birth weight, gestational age (weeks) and labour length.

  2. b

    Odds of event for LSFP or HSFP/Odds of event for NFP.

  3. c

    Data missing for 31 and 5 cases of LSFP and HSFP, respectively.

  4. d

    Not calculated for HSFP due to a single case in this group.

  5. NFP, non-febrile parturients; LSFP, low subfebrile parturients; HSFP, high subfebrile parturients; OR, odds ratio; aOR, adjusted odds ratio; CI, confidence interval; NICU, neonatal intensive care unit.

Primary caesarean1.78[1.63, 1.94]1.26[1.15, 1.38]4.35[3.76, 5.04]2.01[1.72, 2.36]
Assisted Vaginal Delivery1.60[1.47, 1.73]1.16[1.08, 1.27]3.30[2.82, 3.85]1.43[1.21, 1.68]
Apgar 1 min ≤4c2.17[1.46, 3.23]2.06[1.38, 3.07]1.92[0.78, 4.79]1.80[0.72, 4.51]
Apgar 5 min ≤7c1.70[1.12, 2.59]1.63[1.07, 2.49]1.48[0.54, 4.09]1.42[0.51, 3.93]
NICU admission1.62[1.24, 2.10]1.48[1.13, 1.93]0.84[0.37, 1.91]0.81[0.36, 1.85]
Neonatal asphyxia or seizuresd4.07[1.93, 8.61]3.49[1.64, 7.39]
Neonatal sepsis2.63[1.82, 3.78]2.45[1.70, 3.54]4.70[2.58, 8.56]4.24[2.31, 7.80]

We further incorporated all outcomes into two main composite outcomes: (1) operative delivery, including caesarean sections and assisted vaginal deliveries, and (2) neonatal morbidity, including all adverse neonatal outcomes (low Apgar scores, NICU admissions, early neonatal sepsis, convulsions, and asphyxia). A multivariate analysis revealed a 1.2 and 1.71 increased risk for operative delivery for LSFP and HSFP, respectively (P < 0.01) and a 1.69 and 1.80 increased risk for neonatal morbidity for LSFP and HSFP, respectively (P < 0.01).

A subanalysis stratified by parity is presented in Table 4. Increased risks for caesarean section and early neonatal sepsis were demonstrated in both groups. However, associations with assisted vaginal deliveries, low 1-min Apgar score, neonatal asphyxia, or seizures, and NICU admissions were statistically significant only among nulliparous parturients.

Table 4. A subanalysis: Obstetrical and neonatal outcomes of nulliparous and multiparous parturients with intrapartum subfebrile temperature
 NulliparousMultiparous
SFP (N = 5458)LSFP (N = 4451)HSFP (N = 1007)SFP (N = 6090)LSFP (N = 5724)HSFP (N = 366)
OutcomeaaORb95% CIaORb95% CIaORb95% CIaORb95% CIaORb95% CIaORb95% CI
  1. a

    Odds of event for SFP, LSFP or HSFP/Odds of event for NFP.

  2. b

    Primary C/S and assisted vaginal delivery models adjusted for: age, gestational age (weeks), epidural and labour length; Apgar scores, NICU admissions, neonatal asphyxia or convulsions and neonatal sepsis models adjusted for: Epidural, birth weight, gestational age (weeks) and labour length.

  3. c

    N/A, Not Available: Not calculated due to 0 or 1 cases.

  4. NFP, non-febrile parturients; SFP, subfebrile parturients; LSFP, low subfebrile parturients; HSFP, high subfebrile parturients; aOR, adjusted odds ratio; CI, confidence interval; C/S, caesarean section; NICU, neonatal intensive care unit.

Primary C/S1.40[1.25, 1.56]1.27[1.13, 1.44]2.01[1.68, 2.39]1.33[1.15, 1.54]1.27[1.09, 1.48]2.31[1.57, 3.39]
Assisted vaginal delivery1.25[1.14, 1.38]1.22[1.10, 1.35]1.45[1.21, 1.73]1.05[0.88, 1.24]1.02[0.86, 1.22]1.41[0.83, 2.39]
Apgar 1 min ≤41.62[0.98, 2.68]1.69[1.01, 2.84]1.27[0.48, 3.35]1.71[0.87, 3.36]1.83[0.93, 3.59]N/AcN/Ac
Apgar 5 min ≤71.14[0.68, 1.92]1.20[0.70, 2.05]0.89[0.31, 2.57]1.62[0.78, 3.33]1.72[0.83, 3.54]N/AcN/Ac
NICU admission1.64[1.12, 2.42]1.77[1.20, 2.62]0.98[0.41, 2.31]1.10[0.74, 1.63]1.16[0.77, 1.72]N/AcN/Ac
Neonatal asphyxia or seizures2.48[0.96, 6.43]3.07[1.19, 7.91]N/AcN/Ac2.62[0.70, 9.76]2.10[0.50, 8.82]N/AcN/Ac
Neonatal sepsis2.04[1.21, 3.41]1.91[1.11, 3.29]2.61[2.22, 5.59]2.55[1.55, 4.17]2.42[1.45, 4.02]4.68[1.43, 15.30]

When comparing the indications for caesarean deliveries between the groups, among SFP 37.6% of caesarean deliveries were due to dysfunctional labour, compared with 17.7% in the NFP group (P < 0.001). The rates of caesarean deliveries due to dysfunctional labour in the LSFP and HSFP groups were 33.4% and 52.0%, respectively (P < 0.001).

Comment

  1. Top of page
  2. Abstract
  3. Methods
  4. Statistical analysis
  5. Results
  6. Comment
  7. References
  8. Supporting Information

In this study, intrapartum subfebrile maternal temperatures of 37.1–37.9°C were associated with adverse obstetric and neonatal outcomes. Subfebrile temperature was significantly associated with higher rates of primary caesarean sections and assisted vaginal deliveries with aOR of 1.36 and 1.20, respectively, with a suggestive dose response with increasing temperature. Similarly, subfebrile temperature was associated with increased risks of low Apgar scores, NICU admissions, neonatal asphyxia or seizures and early neonatal sepsis, with aOR of 1.40-3.18; however, there was no clear trend with increasing temperature. Furthermore, when introducing all outcomes into two main categories, operative delivery and neonatal morbidity, a clear effect of subfebrile intrapartum temperature was demonstrated. The associations were prominent especially among nulliparous parturients.

There are only a few studies on the association of intrapartum febrile temperature and obstetric outcomes; these studies demonstrated an increased risk of operative deliveries among women with fever.[5, 14] In one of these studies, which included 1233 nulliparous women with singleton term pregnancies, temperature elevation was associated with a double risk of caesarean and assisted vaginal deliveries.[5] Other studies found an association between epidural analgesia and increased body temperature.[9, 10, 15, 16] Gonen et al. demonstrated a statistically significant association between the duration of the epidural block and the development of intrapartum fever.[10] Because epidural analgesia and prolonged labour are associated with intrapartum fever, we adjusted our analysis to epidural analgesia and to length of labour. Yet, even after adjustment for these and other confounders, a clear and statistically significant relationship remained between subfebrile temperature during labour and adverse birth outcomes. This finding implies that subfebrile temperature may be an independent risk marker for these outcomes.

In our study, neonates of mothers who experienced subfebrile temperature had a 40% increased risk for NICU admission, a 2.7-fold increased risk of early neonatal sepsis, and a 3.2-fold increased risk for asphyxia or seizures compared with neonates of mothers with normal intrapartum body temperature. Increased risk of these adverse neonatal outcomes was shown even in the LSFP group. Adverse neonatal outcomes, including transient and lasting morbidities in the newborn, were previously related mainly to intrapartum fever. These adverse outcomes have been shown to affect primarily the respiratory and neurologic systems of the newborn, with one study showing an almost threefold risk for bag and mask resuscitation of the newborn of febrile parturients,[2] and another study demonstrating a 3.4-fold increase in the risk of unexplained neonatal seizures in cases of maternal intrapartum fever.[17] Impey et al. showed that intrapartum fever (defined by them as temperature higher than 37.5°C) is associated with an almost fivefold risk for neonatal encephalopathy.[18, 19] The association of maternal infection during labour and risk of cerebral palsy is also well established.[20-22] Yet, in our study we also found adverse perinatal outcomes in the very low subfebrile temperature group.

Our findings of increased risk of early neonatal sepsis may be in contrast to a recent study showing low post-delivery adverse neonatal risks, especially for sepsis, in infants born to mothers with intrapartum fever above 37.8°C.[23] However, the differences may stem from the small study group and different inclusion criteria.

Our findings are in accordance with a recent smaller study that examined only term infants of nulliparous women receiving epidural analgesia.[24] In their study, Greenwell et al. also observed higher risks of low Apgar scores and seizures, as well as hypotonia and need for assisted ventilation.[24] However, these associations were not studied in parturients experiencing intrapartum subfebrile temperature of 37.1–37.4°C. In the subanalysis of the two groups with subfebrile intrapartum temperature, some of the neonatal outcomes were worse in the LSFP group than in the HSFP group. This may reflect a statistical limitation of our study because of the rarity of some of the outcomes studied. Alternatively, given the current routine, LSFP, as opposed to HSFP, do not receive any special clinical attention from the obstetrician in the delivery room or from the neonatologist, yielding worse results in the undiagnosed and untreated group.

When considering the findings of studies that examined fever during labour, it can be claimed that medical staff assesses more frequently parturients with intrapartum fever, that obstetricians are more likely to intervene surgically in these women, and that neonatologists are more likely to evaluate neonates of febrile parturients for sepsis (i.e. confounding by indication). However, because subfebrile temperature is so far not considered as a risk marker for birth complications, it is not associated with changes in clinical practice or approach, therefore, confounding by indication is an unlikely explanation in our study. Our findings suggest that subfebrile temperature may be an independent risk marker for these outcomes, or at least it should alert obstetricians and neonatologists to consider these deliveries as high risk for adverse perinatal outcomes.

Subfebrile intrapartum temperature may be the result of dysfunctional labour, and it may be a sign of an obstructed labour. A possible pathophysiological mechanism is illustrated in Figure 2. Dysfunctional labour due to dystocia may result in elevated levels of pyrogens such as PGE2 or prostaglandin F2 alpha (PGF2A); increased levels of inflammatory cytokines such as interleukin (IL)-1b, IL-6, and IL-8;[25] and high plasma levels of oxytocin (endogenous and exogenous). Any of these conditions may result, either directly or indirectly, in mildly elevated temperature and in modifying the fetal or neonatal inflammatory response, even in the absence of infection.[26-31] This mechanism is supported by previous findings of increased rates of caesarean sections and uterine hyperstimulation in response to PGE2.[32] Uterine hyperstimulation, along with mildly elevated temperature that affects uterine vascular resistance, may result in further decrease of the utero-placental blood flow,[33, 34] which may be associated with increased rates of operative delivery and neonatal morbidity. It should be mentioned that adjusting our findings to oxytocin administration had a trivial effect on the results (data not shown). This theory may also be supported by the lower risk of adverse outcomes in births that are less prone to be complicated with dysfunctional labour such as births of multiparous parturients. Importantly, because this is a retrospective study, the aforementioned hypothesis is speculative and requires verification in prospective and basic science studies.

figure

Figure 2. A proposed mechanism demonstrating the role of subfebrile temperature in an obstructed labour.

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The present study has several limitations. Data for the current analysis were not collected for study purposes, and the analysis was based on routine clinical data management. Therefore, the quality of the data might be reduced. However, this is also one of the study's strengths, namely allowing a large cohort that included all deliveries in two hospitals during a 7-year period. In our study population, only 8% of parturients had missing data on temperature during labour.

To estimate biases that could result from missing maternal temperature recording during labour, we conducted sensitivity analyses in which we imputed temperature levels for all missing values using a random assignment. This sensitivity analysis yielded similar results to our original findings, and the significant association between subfebrile temperature and obstetric and neonatal outcomes remained unaltered (data not shown).

Infrequent temperature measurements may lead to misclassification of temperature groups. SFP may be classified as afebrile, however, such misclassification would bias the results to the null. On the other hand, a concern may rise that SFP who developed a fever that was not detected may have been misclassified as subfebrile. However, maternal intrapartum fever (i.e. temperature ≥ 38.0) is usually accompanied by various clinical signs, such as sweating, shivering, tachycardia, and fetal tachycardia. These signs warrant close obstetric surveillance, and thus missing fever development seems unlikely. Lending support to this assumption, in a file review, only 4.6% of mothers to newborns with neonatal sepsis who were not classified as febrile during labour suffered from puerperal fever.

Another limitation of our study is that we could not assess accurately the severity of subfebrile episodes during labour. Our very large cohort and the clear associations may attenuate this limitation. Additionally and lending support to our results, this method of temperature measurement was used also in few previous studies examining association of intrapartum fever and perinatal outcomes and that had demonstrated similar results.[2, 5]

In conclusion, while the management of maternal fever (temperature ≥ 38°C) during labour is well established and includes reduction of maternal temperature and consideration of an antibiotic treatment, currently, there are no available guidelines as to the management of subfebrile temperature. With the lack of evidence, many physicians do not consider a temperature below 38°C (and even less so below 37.6°C) as a risk marker for either obstetric or neonatal complications that needs to be addressed. Our findings suggest that subfebrile temperature during labour is indeed a risk marker that should be addressed by obstetricians and neonatologists as a sign of dysfunctional labour and neonatal morbidity. Additional research is needed to clarify the mechanism by which mildly elevated temperature is associated with adverse birth outcomes, and to determine the extent to which treatment or even prevention of subfebrile temperature may affect the incidence of adverse obstetric and neonatal outcomes.

References

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  2. Abstract
  3. Methods
  4. Statistical analysis
  5. Results
  6. Comment
  7. References
  8. Supporting Information
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Supporting Information

  1. Top of page
  2. Abstract
  3. Methods
  4. Statistical analysis
  5. Results
  6. Comment
  7. References
  8. Supporting Information
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ppe12090-sup-0001-si.docx55K

Appendix S1. Distribution of study outcomes by temperature groups.

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