Dallas 2015

TFQO: Marilyn Escobedo COI#78EVREV 1: Marilyn Escobedo COI#78EVREV 2: Henry Lee COI#135Taskforce: NRP

Babies born to mothers who are hypothermic or

hyperthermic in laborNRP 804

Dallas 2015

COI Disclosure

EVREV 1 COI# 78 EscobedoCommercial/industry• None

Potential intellectual conflicts• None

EVREV 2 COI#135 LeeCommercial/industry• None

Potential intellectual conflicts • None

Dallas 2015

2010 CoSTR

No review in 2010.

Dallas 2015C2015 PICO

Population: Newborn babiesIntervention: Maternal hypothermia or hyperthermia in labor Comparison: Normal maternal temperature

Outcomes: Adverse neonatal effects 9-Critical Mortality 6-Important Adverse neurological outcome6-Important Incidence of seizures

Dallas 2015Inclusion/Exclusion& Articles Found

InclusionsRCTs, studies with concurrent or historical controls

ExclusionsReviews, animal studies, unpublished studies, abstracts

1426 Number of Articles initially identified, and 22 Finally Included in Evidence Profile tables7 RCTs, 15 non-RCTsRemainder excluded

Dallas 20152015 Proposed Treatment Recommendations

With regard to maternal hyperthermiaAlthough maternal hyperthermia is associated with adverse neonatal outcomes, there is insufficient evidence to make a recommendation on the management of maternal hyperthermia.

With regard to maternal hypothermiaThere is insufficient evidence to make a recommendation about maternal hypothermia.

There are no randomized controlled trials of important or critical neonatal outcomes after interventions to keep mothers normothermic.

Dallas 2015 Risk of Bias in studies

Dallas 2015 Risk of Bias in studies

Dallas 2015 Key data from key studies

First Author YearRCT or Non-RCT

Intervention

Measured

Outcome Measured

Loss to Follow-up?

Intervention or Control?

Number with

Outcome

Total Number

Number with

Outcome

Total Number

Notes relevant to the outcome

Alexander 1999Non-RCT

Maternal hyperthermia = or >38C

neonatal death none 3 5144 36 96026

Retrospective chart review of term infants >2500 g 1988-1997. After adjustment for confounders, intubation, pneumonia and sepsis (but not death) were related to maternal fever.

Petrova 2001Non-RCT

Maternal fever = or > 38C

Early neonatal mortality

(term parous) 91 113750 2588 4E+06

Retrospective cohort study of birth certificate data (US) 1995-1997 with socio-demographic and clinical risk adjustment variables - AOR with clinical and sociodemographic variables: 1.05 (0.75, 1.48)

Petrova 2001Non-RCT

Maternal fever = or > 38C

Early neonatal mortality

(term nulliparous) 49 40833 3744 5E+06

AOR with clinical and sociodemographic variables: 1.67 (1.14, 2.46)

Petrova 2001Non-RCT

Maternal fever = or > 38C

Early neonatal mortality

(preterm parous) 566 10404 12478 458750

AOR with clinical and sociodemographic variables: 1.29 (1.01, 1.64)

Petrova 2001Non-RCT

Maternal fever = or > 38C

Early neonatal mortality

(preterm nulliparous) 699 7989 13643 614550

AOR with clinical and sociodemographic variables: 1.32 (1.11, 1.56)

Dallas 2015 Key data from key studies

First Author Year RCT or Non-RCTIntervention

MeasuredOutcome Measured

Loss to Follow-up? Intervention or

Control?Mean

Standard Deviation

Total Number

MeanStandard Deviation

Total Number

Butwick 2007 RCT

Maternal lower body forced air-warming during spinal anesthesia

neonatal apgar scores at 1 minute none 8 15 9 15

Butwick 2007 RCT

Maternal lower body forced air-warming during spinal anesthesia

neonatal apgar score at 5 minutes none 9 15 9 15

Butwick 2007 RCT

Maternal lower body forced air-warming during spinal anesthesia umbilical venous pH none 7.31 0.06 15 7.3 0.04 15

Butwick 2007 RCT

Maternal lower body forced air-warming during spinal anesthesia umbilical arterial pH none 7.26 0.04 15 7 0.07 15

Intervention Group Control Group

Dallas 2015Evidence profile table(s)

Dallas 2015Proposed Consensus on Science statements

Maternal Hyperthermia

•For the critical outcome of mortality we have identified low quality evidence from 2 non-RCT studies showing an increased risk with maternal hyperthermia (Petrova 2001, 20, Alexander 1999, 274)

•For the important outcome of neonatal seizures we have identified low quality evidence from 7 non RCT studies showing an increased risk with maternal hyperthermia (Alexander 1999, 274, Greenwell 2012, e447, Petrova 2001, 20, Goetzel 2010, 363.e1, Glass 2009, 24, Lieberman 2000, 8, Lieberman 2000, 983)

•For the important outcome of other adverse neurological states (encephalopathy) we have identified low quality evidence from 4 non-RCT studies showing an increased risk with maternal hyperthermia (Badawi 1998, 1554, Impey 2001 49.e1, Impey 2008, 594, Linder 2013, 207)

Dallas 2015Proposed Consensus on Science statements

Maternal hypothermia •For the critical outcome of mortality and the important outcomes of seizures or adverse neurologic states (encephalopathy) we have identified very low quality evidence from 5 RCTs that showed no significant risk of these outcomes with maternal hypothermia (Butwick 2007, 1413, Fallis 2002, 324, Horn 2002, 409, Woolnough 2009, 346, Yokohama 2009, 242). However, these studies did not examine the outcomes of mortality, seizures, or adverse neurologic outcome.

Dallas 20152015 Proposed Treatment Recommendations

With regard to maternal hyperthermiaAlthough maternal hyperthermia is associated with adverse neonatal outcomes, there is insufficient evidence to make a recommendation on the management of maternal hyperthermia.

With regard to maternal hypothermiaThere is insufficient evidence to make a recommendation about maternal hypothermia.

There are no randomized controlled trials of important or critical neonatal outcomes after interventions to keep mothers normothermic.

Dallas 2015

Values & Preferences

Although maternal hyperthermia is associated with adverse neonatal outcomes, it remains unclear if interventions to normalize maternal temperature would change those outcomes. Suggesting avoidance of abnormal maternal temperature places value on the possibility of reducing harm.

Dallas 2015Knowledge Gaps

• Do interventions to achieve normothermia in mothers who are hyperthermic decrease risk of adverse outcomes for newborns?

(Lack of RCTs)• Do interventions to achieve normothermia in

mothers who are hypothermic decrease risk of adverse outcomes for newborns?

(Lack of critical / important outcomes)

Dallas 2015Next Steps

This slide will be completed during Task Force Discussion (not EvRev) and should include:

Consideration of interim statementPerson responsibleDue date

Essential slide (one slide only). Estimated time <30 sec