Natural Eating Behavior in Latent Labor and Its Effect on Outcomes in Active Labor

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FEATURE Natural Eating Behavior in Latent Labor and Its Effect on Outcomes in Active Labor Myra Parsons, CNM, John Bidewell, PhD, and Sue Nagy, RN, PhD This study examined the effect of eating during the latent phase of labor on the hospital-estimated labor duration and birth outcomes for the mother and baby. A prospective, comparative trial with concurrent controls compared labor duration and outcomes of 176 low-risk, nulliparous women who birthed at four hospitals in Sydney, Australia. Food was voluntarily consumed by 82 women, whereas 94 consumed clear fluids only. Food intake during the latent phase of the first stage of labor was associated with a longer duration of labor (mean difference 2.35 hours). No difference was found between eating and noneating groups for the rate of medical interventions, adverse birth outcomes, or vomiting. Results suggest that eating during the latent phase of labor may increase labor duration. J Midwifery Womens Health 2006;51:e1– e6 © 2006 by the American College of Nurse-Midwives. keywords: labor, food, eating behavior, birth outcome, labor duration INTRODUCTION Surveys of hospitals, 1–3 midwives, 4 and anesthetists 5 have found disagreement over whether laboring mothers should eat. Many midwives are concerned that fasting or restrict- ing women to clear fluids during labor may compromise birth outcomes. They argue that dietary restrictions during labor could lengthen labor and increase medical interven- tion rates. 4,6–8 On the other hand, anesthetists are con- cerned about the risk of gastric content aspiration if a general anesthetic were required during labor. 5,9 –11 The anesthetists’ argument is based on an understanding of pathophysiology; historic, as opposed to contemporary, drugs and techniques; and, anecdotally, a belief that labor- ing women do not need food or fluids during labor. No research, however, demonstrates that restricting laboring women’s oral intake reduces the incidence of aspiration. According to maternal mortality records over the last 40 to 50 years in the United States, Australia, and the United Kingdom, oral intake during labor has never been cited as a cause or a factor in the incidence of aspiration during obstetric general anesthesia. 12–16 There is no reliable re- search evidence to support either the midwives’ or the anesthetists’ opposing positions regarding the correct di- etary intake policy for laboring mothers. The disagreement between these two professions may be attributed to their differing clinical priorities. Midwives seek to reduce labor duration and medical interventions, whereas anesthetists seek to reduce risk during general anesthesia. Beyond the views of individual practitioners, dietary intake during labor has policy implications for hospitals and providers of maternity services. At an institutional level, there appears to be no consensus about dietary regimens for laboring women. Some hospitals allow laboring women to eat, whereas other hospitals forbid it. 1–3 Research compar- ing labor and birth outcomes in large samples of women according to their eating behavior during labor should be the framework for policy; however, studies in this area are limited in number and their results conflict. 17–20 Database literature searches conducted for the current study revealed a paucity of research relating to oral intake during labor. Other than surveys 1–4 and observational studies, 21,22 only one published randomized controlled trial (RCT) has been conducted to compare laboring women who ate food with those who did not. 18 Three unpublished RCT studies were located. 17,19,20 These four studies have methodological differences that give conflicting findings. One outcome measure reported by these studies, length of labor, was found to be longer, 20 shorter, 17 and the same 18,19 when women ate food during labor compared with those who did not eat, whereas the incidence of medical inter- vention during labor was found to be less 17 and un- changed. 18 –20 All four RCTs required all women in a designated eating group to eat food during the active phase of labor, whereas women in the noneating group were expected to refrain from food. Anecdotally, midwives have found that most women are disinclined to eat during active labor. Requiring women to eat lends a degree of artificiality to these studies. The current study addresses the absence of research into the effect of natural eating behavior on labor and birth outcomes. A prospective, comparative design with concur- rent controls was used to compare active labor duration and birth outcomes for mothers on the basis of volitional eating during latent labor. Address correspondence to Myra Parsons, CNM, University Western Sydney, C/- 23 Mansfield Road, Galston NSW 2159, Australia. E-mail: [email protected] Journal of Midwifery & Women’s Health www.jmwh.org e1 © 2006 by the American College of Nurse-Midwives 1526-9523/06/$32.00 doi:10.1016/j.jmwh.2005.08.015 Issued by Elsevier Inc.

Transcript of Natural Eating Behavior in Latent Labor and Its Effect on Outcomes in Active Labor

Page 1: Natural Eating Behavior in Latent Labor and Its Effect on Outcomes in Active Labor

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FEATURE

Natural Eating Behavior in Latent Labor and Its Effect onOutcomes in Active LaborMyra Parsons, CNM, John Bidewell, PhD, and Sue Nagy, RN, PhD

This study examined the effect of eating during the latent phase of labor on the hospital-estimated laborduration and birth outcomes for the mother and baby. A prospective, comparative trial with concurrentcontrols compared labor duration and outcomes of 176 low-risk, nulliparous women who birthed at fourhospitals in Sydney, Australia. Food was voluntarily consumed by 82 women, whereas 94 consumed clearfluids only. Food intake during the latent phase of the first stage of labor was associated with a longerduration of labor (mean difference � 2.35 hours). No difference was found between eating and noneatinggroups for the rate of medical interventions, adverse birth outcomes, or vomiting. Results suggest that eatingduring the latent phase of labor may increase labor duration. J Midwifery Womens Health 2006;51:e1–e6© 2006 by the American College of Nurse-Midwives.

keywords: labor, food, eating behavior, birth outcome, labor duration

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NTRODUCTION

urveys of hospitals,1–3 midwives,4 and anesthetists5 haveound disagreement over whether laboring mothers shouldat. Many midwives are concerned that fasting or restrict-ng women to clear fluids during labor may compromiseirth outcomes. They argue that dietary restrictions duringabor could lengthen labor and increase medical interven-ion rates.4,6–8 On the other hand, anesthetists are con-erned about the risk of gastric content aspiration if aeneral anesthetic were required during labor.5,9–11 Thenesthetists’ argument is based on an understanding ofathophysiology; historic, as opposed to contemporary,rugs and techniques; and, anecdotally, a belief that labor-ng women do not need food or fluids during labor. Noesearch, however, demonstrates that restricting laboringomen’s oral intake reduces the incidence of aspiration.ccording to maternal mortality records over the last 40 to0 years in the United States, Australia, and the Unitedingdom, oral intake during labor has never been cited ascause or a factor in the incidence of aspiration during

bstetric general anesthesia.12–16 There is no reliable re-earch evidence to support either the midwives’ or thenesthetists’ opposing positions regarding the correct di-tary intake policy for laboring mothers. The disagreementetween these two professions may be attributed to theiriffering clinical priorities. Midwives seek to reduce laboruration and medical interventions, whereas anesthetistseek to reduce risk during general anesthesia.

Beyond the views of individual practitioners, dietaryntake during labor has policy implications for hospitals and

ddress correspondence to Myra Parsons, CNM, University Western

dydney, C/- 23 Mansfield Road, Galston NSW 2159, Australia. E-mail:[email protected]

ournal of Midwifery & Women’s Health • www.jmwh.org2006 by the American College of Nurse-Midwives

ssued by Elsevier Inc.

roviders of maternity services. At an institutional level,here appears to be no consensus about dietary regimens foraboring women. Some hospitals allow laboring women toat, whereas other hospitals forbid it.1–3 Research compar-ng labor and birth outcomes in large samples of womenccording to their eating behavior during labor should behe framework for policy; however, studies in this area areimited in number and their results conflict.17–20

Database literature searches conducted for the currenttudy revealed a paucity of research relating to oral intakeuring labor. Other than surveys1–4 and observationaltudies,21,22 only one published randomized controlled trialRCT) has been conducted to compare laboring womenho ate food with those who did not.18 Three unpublishedCT studies were located.17,19,20 These four studies haveethodological differences that give conflicting findings.ne outcome measure reported by these studies, length of

abor, was found to be longer,20 shorter,17 and the same18,19

hen women ate food during labor compared with thoseho did not eat, whereas the incidence of medical inter-ention during labor was found to be less17 and un-hanged.18–20 All four RCTs required all women in aesignated eating group to eat food during the active phasef labor, whereas women in the noneating group werexpected to refrain from food. Anecdotally, midwives haveound that most women are disinclined to eat during activeabor. Requiring women to eat lends a degree of artificialityo these studies.

The current study addresses the absence of research intohe effect of natural eating behavior on labor and birthutcomes. A prospective, comparative design with concur-ent controls was used to compare active labor duration andirth outcomes for mothers on the basis of volitional eating

uring latent labor.

e11526-9523/06/$32.00 • doi:10.1016/j.jmwh.2005.08.015

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he trial used a convenience sample of English-speaking,ow-risk, nulliparous women who were scheduled to giveirth at any of four public hospitals in Sydney, Australia,ver a 7-month period. The four hospitals had similar birthates, and all had a multicultural clientele. The study wasestricted to nulliparous women because their labors tend toe longer, and they are more likely to require medicalnterventions than multiparous women.23 Participants weredentified and enrolled during the last 4 weeks of theirregnancy. At the time of enrollment, each woman wasiven a survey form to be completed throughout her labornd instructions to record the time her labor contractionsommenced and all foods and fluids consumed.

Participants were excluded from the study if their laboras induced by cervical ripening agents, oxytocin infusion,r both, or terminated by cesarean delivery, because theatural length of the hospital-estimated labor cannot bescertained under these circumstances.23

Rather than impose an ethically questionable eatingchedule on women, the current study classified laboringomen into eating and noneating groups according tohether they chose to eat food during the latent phase of

abor. Thus, the chosen design investigates natural ratherhan enforced eating or food abstinence, albeit subject tondividual midwives’ discretion when the women presentedo hospital. Because few women ate food during the activehase of the first stage of labor, either by choice or becauseheir midwife disallowed food (reason unknown), the effectf eating only during the latent phase of the first stage ofabor was explored.

The onset of latent labor is diagnosed by the woman andannot be identified by objective means. Midwives’ esti-ate of the commencement of active labor is based on theoman’s retrospective account of her labor and unverified

ervical assessments. Therefore, an exact measurement ofhe stages of labor is difficult, especially in the absence ofegular cervical assessments from the commencement ofabor. With this limitation in mind, the stages of labor werelassified for this study as follows:

Latent Phase” of the First Stage of Labor

o differentiate between prelabor and the latent phase ofhe first stage of labor, participants were asked to record theime regular contractions commenced in their labor beforeoming to hospital. This time marked the commencement

yra Parsons, CNM, MACMI, is in private practice in Sydney, Australia, anddoctoral candidate at the University of Western Sydney.

ohn Bidewell, PhD, is a research psychologist at the School of Nursing,amily, and Community Health, University of Western Sydney, Australia.

ue Nagy, RN, PhD, FRCNA, is an Adjunct Professor at the University ofechnology Sydney School of Nursing, Midwifery and Health, Sydney. She is

tlso a Research Fellow with the Nursing and Health Services Researchonsortium in Sydney.

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f latent labor. This phase ended when the woman’s cervixas 3 cm dilated. As hourly cervical assessments were noterformed and because some women arrived at the hospitalfter this point in their labor, the end of this phase was oftenpproximated by the midwife in charge of the case usingraditional criteria (i.e., the commencement of regular,ainful contractions 5 minutes apart as reported by theoman).

Hospital-Estimated” Labor

his measurement includes the active phase of the firsttage of labor plus the second stage of labor (i.e., from 3 cmervical dilatation to birth) and excludes the latent phase ofabor measurement. The commencement of active laboras determined by cervical assessment (or estimated if

ervical assessment was not conducted at 3 cm dilatation)nd recorded in the participant’s medical record by theidwife in charge of the case. The time used to mark the

nd of the latent phase was also used to mark the com-encement of the active phase of labor (e.g., latent phase �

200 to 0645 hours; hospital-established labor � 0645ours to birth). The duration of this labor period served asmajor outcome variable for the study.The labor duration of women who chose to eat food

uring the latent phase of the first stage of labor and nother time during labor (“eating group”) was comparedith women who did not eat at any time during labor

“noneating group”). The eating and noneating groupsere compared for labor duration and the following birthutcomes: medical augmentation, artificial rupture ofembranes, intravenous therapy for hydration, meperi-

ine (pethidine) injection, epidural anesthesia for labor,orceps, or vacuum-assisted delivery, estimated maternallood loss, incidence of vomiting, newborn 5-minutepgar score, and admission to a special care nursery.The hospital birth register provided details of the time

ach woman’s active phase of first stage labor commencednd the time of birth, as originally recorded by the midwifen attendance. The register also gave details of maternallood loss, Apgar score, and medical interventions useduring the labor and birth process. Information regardingntravenous therapy and admission to the special careursery was obtained from each woman’s medical record.

survey form developed for this study and completed byhe women or their support persons throughout laborrovided details of the start of the latent phase of labor (theommencement of regular contractions) and the timing,ype, and amount of all oral intake consumed from the onsetf labor until birth.

thics

ritten consent to perform this study was granted by theuman Ethics Committees of all four hospitals and by allarticipants. Anonymity and confidentiality were guaran-

eed for all participants.

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tatistics

ata analysis was performed by using STATISTICAoftware.24 Eating and noneating group demographicsere compared by using t tests (maternal age andestation) and a �2 test (ethnicity) to establish whetherhe groups differed systematically on relevant back-round variables.Participants were classified into eating and noneating

roups on the basis of whether they chose to eat duringhe latent phase of the first stage of labor. Duration of theospital-estimated length of labor was compared be-ween groups to identify overall differences in activeabor duration without controlling for other likely pre-ictors. Next, a hierarchical multiple regression testedhe relationship between eating during latent labor andubsequent labor duration while controlling for otherelevant variables: the duration of latent labor, age,estation, fetal position, and the mother’s ethnic back-round. Fetal position involved a comparison betweenhe occipit-lateral and occipit-posterior positions againsthe occipit-anterior. Asian, Middle Eastern, and Polyne-ian ethnic backgrounds were compared against Cauca-ian. The first stage of the hierarchical regression in-luded all predictors except eating during latent labor.he second stage of the regression added the eatinguring latent labor variable to determine its incrementalffect and significance as a predictor of the hospital-stimated labor duration.

The possibility of interactive effects between eatinguring latent labor and fetal position on subsequent laboruration was explored by using factorial ANCOVA,hich controlled for other continuous predictors: latent

abor duration, gestation, and maternal age.The effect of eating during latent labor on the inci-

ence of adverse labor and birth outcomes was examinedia �2 tests and discriminant analyses. The �2 testsompared percentages of the eating and noneatingroups experiencing the adverse outcome. A multivariateiscriminant analysis tested for differences between eachabor and birth intervention and outcome for the tworoups while controlling for the incidence of otherutcomes and background variables. This analysis waserformed by using 147 subjects after the removal of 29ubjects with missing data for the position of the fetusuring labor. Eating and noneating group differences forhe 5-minute Apgar score and for maternal blood lossere also tested with the univariate Mann-Whitney test,ased on ranks, and suitable for ordinal variables, alongith the better known t test comparing the means.Statistical power analysis found a 90% chance of a

ignificant result from an independent t test for aopulation effect size of 0.5 SD with n � 86 per group,

o the design had adequate power. e

ournal of Midwifery & Women’s Health • www.jmwh.org

ESULTS

ample Description and Eating Behaviors

hree hundred thirty-one low-risk, nulliparous, English-peaking women consented to and were enrolled in thetudy from the four hospitals consecutively. Of these, 103ere excluded because of induction of labor, caesareanelivery, or both. Another 11 women were excluded fromhe study because data regarding the commencement of theatent phase of labor (as recorded by the women) conflictedith the time recorded by the midwife for the commence-ent of the active phase of labor. Another 41 women were

lso excluded because they ate food during the active phasef labor (10 women ate during the active phase of labornly, and 31 women ate during both the latent and thective phases). The final sample for analysis was 176.

The eating and noneating groups had similar ethnicompositions (P � .62). Women in the eating group werelder in years than those from the noneating group (P �04), although the difference is not clinically relevant. Meanestation in weeks was effectively the same for both theating group and noneating group (P � .56) (Table 1).

Twenty-three percent of the eating group consumed fulleals during the latent phase of labor (e.g., meat and

egetable, pasta with sauce, meat pies, fish and chips, andast food meals). The remaining 77% consumed lighteals, such as toast, sandwiches, soup, cereal with milk, ice

ream, and yogurt. The noneating group (n � 94) con-umed clear fluids, such as water, fruit juice, tea, or coffee.

Twenty-eight percent of the eating group and 30% of theoneating group vomited during labor (any phase). Thencidence of vomiting was unrelated to whether a womante during the latent phase of labor (P � .80).

omparison of Labor Between Groups

he latent phase of the first stage of labor was significantlyonger, more than twice the length, among the women whote food during this phase compared with those who did not

Table 1. Eating and Noneating Group Sample Description (N � 176)

Eating Group(n � 82)

NoneatingGroup (n � 94)

thnicity (%)European 76 74Asian 12 14Polynesian (Maori andIslander)

2 5

Middle East 10 7ge (y)*

Mean (SD) 25.59 (4.49) 24.11 (5.39)estation at birth (wk)

Mean (SD) 39.91 (1.01) 39.82 (1.11)

P � .05.

at (P � .001). Women who ate during the latent phase also

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xperienced a longer hospital-estimated labor length (P �001). Table 2 shows that the noneating group experiencedhospital-estimated labor duration, on average, 2.35 hours

horter than the eating group.By using multiple regression to control for likely predic-

ors of the hospital-estimated labor duration other thanating, it was found that only fetal position significantlyredicted subsequent labor duration (P � .006). Age, latentabor duration, ethnicity (Asian, Polynesian, Middle East-rn, and Caucasian), and gestation did not predict theospital-estimated duration over and above the other pre-ictors in this model. For this initial model, the fiveredictors listed above collectively accounted for only 9%f the hospital-estimated labor duration variance.The second stage of the analysis added the eating group

ariable, which recorded whether the mother ate duringatent labor. Adding this variable increased the predictionf the hospital-estimated labor significantly (P � .05); theating factor accounted for an additional 6% of the hospital-stimated labor duration. The only significant predictors forhe second-stage model were eating during latent labor andhe occipit-posterior fetal position compared with occipit-nterior. Eating during latent labor added almost 2 hours tohe hospital-estimated labor duration, and the occipit-osterior position added an average of more than 3.5 hours.aternal age; gestational age; occipit-lateral fetal position

ompared with occipit-anterior; and Asian, Polynesian, oriddle Eastern ethnicity compared with Caucasian had no

ignificant direct effects on subsequent labor duration. It ismportant that the apparent effect of eating during latentabor on subsequent labor duration was maintained whenhe regression analysis controlled for other predictors.ating during latent labor was associated with an increasedospital-estimated labor duration independent of other mea-ured factors in this study. A separate ANOVA found thatating during latent labor did not interact significantly withetal position to affect the hospital-estimated labor whileontrolling for latent labor duration, maternal age, andestation period (P � .15). Therefore, the effects of eatinguring latent labor and of the occipit-posterior position onubsequent labor duration were effectively independent.

Table 2. Duration (h) of the Latent Phase and Hospital-EstimatedLabor (Active Phase � Second Stage) for Eating and NoneatingGroups

Phase of LaborEating Group

(n � 82)Noneating Group

(n � 94)

atent phase (h)*Mean (SD) 8.52 (8.31) 4.05 (6.79)Median (Min, Max) 6.00 (0, 38.5) 1.42 (0, 48.5)

ospital-estimated labor*Mean (SD) 9.75 (4.40) 7.40 (2.97)Median (Min, Max) 9.37 (2.20,22.82) 7.31 (2.17,16.27)

P � .001.

Table 3 shows the percentage of the eating and noneating o

4

roups experiencing adverse outcomes during the hospital-stimated length of labor. Although �2 tests found theating group had a significantly higher rate of artificialembrane rupture, the discriminant analysis multivariate

ests, which controlled for other variables in the analysis,ound no significant unique relationship between eatinguring latent labor and any adverse outcome. There were noignificant differences between the eating and noneatingroups for the 5-minute Apgar score and estimated bloodoss. Apgar score means were almost identical for theating and noneating groups, and the estimated blood losseans differed by less than 0.1 SD, consistent with the

bsence of significant differences.

ISCUSSION

his study explored the effect of voluntary food intake byulliparous women during the latent phase of the first stagef labor on their subsequent labor and birth outcomes.ajor findings were that eating during the latent phase of

he first stage of labor was associated with a longerospital-estimated labor duration. Eating during the latenthase of labor and the occipit-posterior position of the fetusere the only variables associated with increased laboruration independent of other factors. The rate of medicalntervention and birth outcomes were unrelated to foodonsumption during labor.

A possible explanation for the association found betweenating and a longer labor is that a portion of the bloodupply that would have assisted uterine contractility mayave been diverted to the stomach for digestion of food.25

lthough a theoretical possibility, this assumption has noteen tested.The position assumed by the fetus during labor is known

o affect labor duration.26 The association between foodonsumption and labor duration, however, is ambigu-

Table 3. Subsequent Labor and Birth Outcomes Compared for theLatent Phase of Labor Eating and Noneating Groups

Eating(n � 82)

n (%)

Noneating(n � 94)

n (%)

edical augmentation 25 (30) 17 (18)rtificial membrane rupture 36 (44) 24 (26)*

ntravenous hydration 13 (16) 11 (12)pidural 10 (12) 11 (12)ethidine 46 (56) 49 (52)omiting 10 (12) 20 (21)orceps or ventouse 19 (23) 15 (16)CN admission 4 (5) 7 (7)-Minute Apgar score, mean (SD) 8.99 (0.60) 8.97 (0.69)aternal blood loss, mL, mean (SD) 241.98 (148.84) 234.57 (121.16)

P � .05 in univariate analyses; no associations were statistically significant inultivariate analyses using a sample size of 147 after removal of 29 subjects withissing data for fetal position in labor.

us.17–20 One RCT20 and the results from this study suggest

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hat eating has the effect of lengthening labor. However, thetage of labor studied differs, with this study using foodonsumption during the latent phase of the first stage ofabor as the independent variable, whereas the active phaseas used in the previous studies.17–20

Some midwives do not allow laboring women to con-ume food because they believe this will cause vomiting.4

his study has shown that when women are permitted tohoose their oral intake, there is no difference in the rate ofomiting between those who eat during latent labor andhose who do not. The increased incidence of vomitingmong the eating groups in past studies may have resultedrom laboring mothers being encouraged to eat contrary toheir desire because of experimental group allocation.18,20

For a clinician to deny a hungry laboring woman food isot an easy decision. Denying food in this situation isnown to be stressful for these women.25 This study foundo compelling evidence to support eating during labor forny reason other than the woman’s wishes. Eating duringatent labor did not improve any of the measured outcomesnd brought a slight increase in subsequent labor duration.his finding, along with anesthetists’ concern about aspi-

ation during general anesthesia, precludes any generalecommendation that laboring women should eat. How-ver, if a woman in the latent phase of labor is hungry andas no sign of complication that could require generalnesthesia, the current data offer no grounds for theidwife to object to the woman eating.This study’s findings were limited by an inability to

ccurately assess a number of outcome measures, such ashe exact timing of the commencement and completion ofhe latent phase of the first stage and commencement of thective phase of the first stage of labor. The commencementf the latent phase of labor depended on the mother’setrospective assessment, whereas the completion time ofhis phase, which also marked the commencement of thective phase, often relied on midwives’ subjective estimateather than cervical examination findings. However, be-ause midwives had no knowledge of the study hypothesis,he inaccurate measurement is unlikely to produce differ-ntial bias in the findings. Maternal blood loss and fetalosition were two other outcome variables that also de-ended on subjective estimates made by clinicians.Future studies could examine volitional eating during the

ctive phase of the first stage of labor. Other studies couldnvestigate how various amounts and types of food affectabor duration, yielding dose-response data indicating sen-ible limits to eating for laboring mothers. Some foodroups may be more appropriate for laboring mothers thanthers. Food characteristics, such as energy density, bulk,peed of digestion and glycemic index may influence birthutcomes differently. Therefore, some types and quantitiesf food, but not others, may be appropriate for someothers during latent labor.The current study has found that eating during the latent

hase of the first stage of labor may increase labor duration

ournal of Midwifery & Women’s Health • www.jmwh.org

hile not affecting birth outcomes. However, given thessues with measurement, and the possibility of unmeasureddditional variables, other causes that may influence theength of labor cannot be ruled out, and one cannot say withonfidence that eating in latent labor causes a longer activetage. Exactly how eating influences labor duration remainsnresolved. Although the current research cannot argue forn outright ban on eating during labor, we recommend thatomen eat in limited quantities until it is demonstrated that

arger amounts are safe, and they should eat only if theyhow no sign of complications that may require surgicalntervention.

Financial support was provided by the University of Western Sydney and theNew South Wales Midwives Association. The authors thank the women whoparticipated, the midwives who assisted with recruitment, and Dr. Pat Brodiefor her critical review and support during the study.

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Volume 51, No. 1, January/February 2006