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ORIGINAL ARTICLE

Risk factors for macrosomia in infants born to Latina womenJM Wojcicki1, NA Hessol2,3, MB Heyman1 and E Fuentes-Afflick1,4

1Department of Pediatrics, University of California, San Francisco, CA, USA; 2Department of Clinical Pharmacy, University ofCalifornia, San Francisco, CA, USA; 3Department of Medicine, University of California, San Francisco, CA, USA and 4Department of

Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

Objective:To assess risk factors for macrosomic infant birth among Latina

women.

Study Design: Prospective study of Latina women recruited during

pregnancy from prenatal clinic at San Francisco General Hospital.

Information was obtained through a structured interview and review of

medical records.

Result:A total of 11% of women delivered macrosomic infants (birth

weight >4000 g). In unadjusted analyses, significant risk factors for

macrosomia included older maternal age, increasing gravidity, previous

history of macrosomic birth and pre-pregnancy overweight. After

adjusting for confounders using multivariate analyses, older mothers

(10-year increments) had an elevated risk of macrosomia

(odds ratio (OR) 2.59; 95% confidence interval (CI) 1.28 to 5.24).

Conclusion:Efforts to reduce macrosomia in Latina women should

focus on older mothers.Journal of Perinatology(2008) 28, 743 749; doi:10.1038/jp.2008.94;

published online 3 July 2008

Keywords: macrosomic birth; nutrition in pregnancy; Latina women;obesity; overweight

Introduction

In 2004, 8.5% of all United States (US) births were high birthweight (X4000 g).1 Macrosomic infants (defined as birth weight>4000 g using a standard cut point from the American College of

Obstetricians and Gynecology Practice Bulletin on FetalMacrosomia) have a greater risk for delivery complications such asshoulder dystocia, brachial plexus injury, clavicular fracture,meconium aspiration and perinatal asphyxia2 as compared toinfants of average birth weight (defined as 2500 to 4000 g).

Macrosomic infants also have a greater risk for overweight,obesity and diabetes mellitus during childhood and adulthood.

Data from the Centers for Disease Control and Preventions (CDC)Pediatric Nutrition Surveillance longitudinal study demonstratesthat children who were macrosomic at birth have a high

prevalence of overweight during childhood (defined as body massindex (BMI) X95th percentile); one-third of macrosomic infants

are overweight at age 3 to 4 years.3 Domestic and internationallongitudinal studies have demonstrated that higher birth weightincreases the risk for adulthood obesity by a factor of 1.5 to 2.4 6

Overweight in childhood and obesity in adulthood areimportantbecause of associationswith the metabolic syndrome7 andcardiovascular disease.8

Previous epidemiologic studies have identified a number ofmaternal risk factors for macrosomic infant birth. These includeolder age (>40 years), tall height (X165 cm), high pre-

pregnancy BMI (BMIX30), nonsmoking, preexisting andgestational diabetes mellitus(GDM), high gravidity, and prolonged

gestation (>41 weeks).914

Small studies have also identifiedexcessivegestational weight gain as a risk factor for macrosomicbirth.15,16

US population data suggest that ethnicity may interact with knownmaternal risk factors and influence the incidence of macrosomicbirth.1 The CDCs National Natality Vital Statistics indicate that theincidence of macrosomic birth amongLatinas (7.9%) is lower thanthe incidence among whites (10.0%).1 Among Latino births, infantsborn to Mexican-origin mothers had a macrosomic rate of 8.5% andinfants born to Central and South American-origin mothers had alower rate (7.8%). These national data are consistent with a study ofthe Northern California Region of Kaiser Permanentes Medical CareProgram, where Latina women had a 30% lower risk of macrosomiathan White women.12 It is surprising that Latinas have a lower rate ofmacrosomia than White women because Latinas have a higherincidence of certain risk factors for macrosomia (gestational diabetes,high pre-pregnancy BMI). However, the lower incidence ofmacrosomia among Latinas suggests that there may be protective

factors such as environmental, behavioral or biologic factors that arespecific to Latinas.1719

The objective of the current study was to evaluate the relation-ship between maternal characteristics and the risk of macrosomiain Latina women in a general population of pregnant women.

Received 22 October 2007; revised 13 May 2008; accepted 2 June 2008; published online

3 July 2008

Correspondence: Dr E Fuentes-Afflick, Department of Pediatrics, Room 6D37, University of

California, 1001 Potrero Avenue, San Francisco, CA 94110, USA.

E-mail: efuentes@sfghpeds.ucsf.edu

Journal of Perinatology (2008) 28, 743749

r 2008 Nature Publishing Group All rights reserved. 0743-8346/08 $30

www.nature.com/jp

http://dx.doi.org/10.1038/jp.2008.94mailto:efuentes@sfghpeds.ucsf.eduhttp://www.nature.com/jphttp://www.nature.com/jpmailto:efuentes@sfghpeds.ucsf.eduhttp://dx.doi.org/10.1038/jp.2008.94

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MethodsStudy design

From July 1997 to September 1999, 350 pregnant Latina womenwere recruited from the prenatal clinic at San Francisco General

Hospital, the only public hospital in San Francisco County. Womenwere recruited atX20 weeks gestation and followed prospectivelyto delivery, as previously described.20 In this study, we definedLatina women as women who self-identified as Latina. Data werecollected during one prenatal, structured interview that includedquestions about health history, diet and sociodemographics.Questions were asked about previous history of diabetes mellitus,GDM in this pregnancy and other health conditions. Interviews

were conducted by three bilingual, bicultural research assistantsand were conducted at a mean gestational age of 31.25.6 weeks.Infant birth weight was abstracted from the nursery logbook andmeasured by a digital scale following delivery, clamping and

cutting the umbilical cord. Maternal pre-pregnancy weight wasobtained by self-report and BMI (kg/m2) was calculated usingself-reported pre-pregnancy weight and measured height. BMI4000 and >4500 g).22We chose the >4000 g cut point (grade 1macrosomia) so that we could compare our results with some ofthe larger cohort studies that use this cut point.9,10,14 We alsoevaluated risk for higher infant birth weight using birth weight asa continuous variable (in increments of 100 g).

The primary independent variable in these analyses was pre-

pregnancy BMI. Other independent variables were maternal age,number of pregnancies (gravidity), history of previous macrosomicbirth, self-reported history of diabetes and hypertension, andnutritional factors. The nutritional factors included consumption of

fresh fruit, vegetables, American food (defined as spaghetti,potatoes and fast food), use of prenatal vitamins and prenatal ironsupplements, and advice about what to eat. Questions on foodconsumption during pregnancy were asked using food frequencymethods adapted from alarger food screener questionnairedeveloped by Blocket al.23 and validated against dietary recallmethods (frequency defined as during the last week and

throughout the pregnancy) with the categories of never, 1 to 3 days

per week, 4 to 6 days per week, everyday, and two times a day.Beverage consumption (soda and coffee) during the last week andthroughout the pregnancy was also ascertained using the followingcategories: none-3 cups per day. We asked

women whether they received advice about what to eat duringpregnancy from their family, friends or health professionals, andthis information was coded as a dichotomous variable. In addition,

we consideredtwo infant factors known to be associated withmacrosomia:10 sex and gestational age. Gestational age wascategorized as 40 weeks. We used the

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language use, cultural self-identification and years lived in theUnited States, we did not find any statistically significantassociation with macrosomia. However, our results trended in thedirection toward indicating that acculturation was associated witha reduced risk of macrosomia. Women who considered themselves

very American were less likely to have macrosomic infants (3.5%)than women who considered themselves Latina (11.6%, P 0.21).

We also found a lower rate of macrosomia (6.8%) among womenwho had some English speaking skills in comparison with thosewho predominately spoke Spanish (11.5%) but our results were notstatistically significant (P 0.36; Table 2).

In unadjusted analyses, one sociodemographic factor wassignificantly associated with macrosomic infants: maternal age(odds ratio, OR 3.09, 95% confidence interval, CI 1.80 to 5.32;Table 2). In addition, pre-pregnancy obesity (OR 3.05, 95% CI 1.22to 7.63), high gravidity (>2 previous pregnancies, OR 2.56, 95% CI1.29 to 5.11) and a previous history of macrosomic birth (OR 5.46,95% CI 2.66 to 11.23), were also associated with an elevated risk ofmacrosomia. Infant gestational age >40 weeks neared statisticalsignificance (OR 2.02, 95% CI 0.96 to 4.25) compared to infants

who were 38 to 40 weeks at time of delivery. Although maternalhistory of pre-pregnancy diabetes mellitus, any diabetes history

(including GDM), maternal height and male infant sex all

Table 1 Mean, standard deviation and frequencies for selected characteristicsamong 348 Latina women, San Francisco, CA, 19971999

Mean Standard

deviation

% (n/total)

Maternal characteristics

Age (years) 25.3 6.0

Pre-pregnancy weight (kg) 62.5 12.3

Height (cm) 155.0 6.2

Gravidity 2.5 1.6

Prior history of diabetes mellitus or

diabetes mellitus with this pregnancy

4.9 (17/348)

History of preexisting hypertension 6.6 (23/348)

Maternal birthplace

USA 5.2 (18/348)

Mexico 56.3 (196/348)

Central/South America 38.5 (134/348)

Maternal pre-pregnancy BMI (kg/m2)

Underweight/normal (

Spanish/only English

6.8 (3/44) 1.00

Self-identification

Very Latina/mostly Latina 11.6 (37/319) 3.67 (0.49 27.80)

LatinaAmerican/mostly

American/very American

3.5 (1/29) 1.00

Maternal origin

Mexico 13.8 (27/196) 2.05 (0.984.27)

Central/South America/United States 7.2 (11/152) 1.00

Maternal health and reproductive

characteristics

Height (cm) 1.57 (0.912.73)c

139.0148.9 5.7 (3/53)

149.0158.9 11.5 (22/192)

159.0168.9 11.8 (9/76)

169.0178.9 25.0 (2/8)

Pre-pregnancy BMI (kg/m2)

Underweight or normal ( 2 16.6 (23/139) 2.56 (1.295.11)

History of diabetes mellitus or

gestational diabetes in this pregnancy

No 10.3 (34/329) 1.00

Yes 17.7 (3/17) 1.81 (0.50 6.62)

Risk factors for macrosomiaJM Wojcicki et al

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conveyed an elevated risk of macrosomia, none were statisticallysignificant. A few dietary factors approached statistical significance;iron supplements, soda and American food consumptionconferred a lower risk of macrosomia but the confidence intervalsspanned unity.

In multivariate regression analyses, maternal age (measured in10-year increments) was the only maternal characteristic that was

statistically associated with increased odds of macrosomic birth(OR 2.59, 95% CI 1.28 to 5.24; Table 3). In addition, femaleinfants were half as likely to be macrosomic as male infants. When

we changed the outcome to birth weight measured as a continuousvariable and used the same variables presented inTable 3in amultivariate model, we found that higher infant birth weight wasassociated with male sex, higher maternal BMI groups and longergestation (results not shown).

Discussion

In this cohort study of pregnant Latina women in San Francisco

recruited without reference to any specific health care need, therate of macrosomic infant birth (10.9%) was approximately 27%higher than the national rate for Latinas (7.9%), although thenational rate uses a slightly different cut point (X4000 g),1 incomparison with the >4000 cut point used by American College ofObstetricians and Gynecologists. The 1-g difference in cut point isnot likely to explain the difference in incidence of macrosomia.The higher rate of macrosomia in our population of Latina womenis surprising because nearly all the women in our study were

foreign-born, and foreign-born Latina women have fewer riskfactors for macrosomic birth, including lower intake of fast food,24

ratio of fat to total energy intake25

and total caloric intake.26

Table 2 Continued

Rate of macrosomia

% (n/N)aOR

(95% CI)b

History of hypertension

No 10.9 (37/340) 1.00

Yes 14.3 (1/7) 1.37 (0.16 11.65)

History of macrosomic birth

No 7.2 (21/291) 1.00

Yes 29.8 (17/57) 5.46 (2.66 11.23)

Maternal nutrition characteristics

Soda consumption during pregnancyd

None/

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Furthermore, the women in our study had a relatively lowprevalence of known risk factors such as pre-pregnancy obesity,older age (X40 years) and preexisting diabetes. Thus, there maybe an undetermined biologic or environmental factor formacrosomia associated with our population of Latinas thataccounts for the elevated rate of macrosomia in our study. Previous

studies have analyzed Latinas in a single national origin group(Mexican origin women)27,28 whereas our study evaluated therisk for macrosomic birth among Latinas from several nationalorigin groups.

In this population of Latina women, increasing maternal agewas strongly associated with macrosomia. Our results are consistentwith previous multiethnic studies, although the relationshipbetween maternal age and macrosomia was stronger in our study.

A large, population-based study reported a 40% increase in the oddsof macrosomia in women 35 to 39 years old in comparison with

youngerwomen and a 20% increase in risk for women over

40 years.9

Metabolic changes are known to occur with age, and it

has been hypothesized that there are specific metabolic factors thatstimulate higher fetal growth velocity among pregnant older

women, resulting in a higher risk ofmacrosomic birth, althoughthese factors have yet to be delineated.9 When we assessed infant

birth weight as a continuous variable, we did not find anassociation between maternal age and infant birth weight. It ispossible that advanced maternal age is only associated withincreased risk for macrosomia when infant birth weights areabove a certain threshold (X4000 g). Further study is neededto understand the physiologic basis for the elevated risk ofmacrosomic infants among older Latina women, and to determine

whether there are other interactions between race/ethnicity,age and risk for macrosomia.

In this sample of Latina women, pre-pregnancy BMI wasassociated with an increased odds of macrosomic infant birth butthis relationship was not statistically significant in multivariable

analysis. In a prior study ofa multiethnic population, women whoweighed more than 300 lb29 had a fourfold increase in risk ofmacrosomia, and women in a Danish study who weighed morethan 80 kg (176 lb) had a twofold increase in risk of macrosomia14

in comparison with normal weight women. Similarly, in a small,multiethnic sample of women with gestational diabetes mellitus,

pre-pregnancy weight was correlated with infant weight.16 We mayhave had insufficient power to detect a statistical difference in risk

for macrosomic birth as a function of pre-pregnancy weight as wehad a relatively small number of obese women (n 60). Inaddition, as pre-pregnancy weight was self-reported and not

confirmed by medical chart review, it is possible that theseresults are subject to recall bias. However, it is also possiblethat pre-pregnancy BMI may be less important as a determinantof macrosomic birth among nondiabetic Latina women, althoughthis hypothesis must be tested in subsequent studies.

We also found an increased risk for macrosomic birth amongLatinas with self-reported preexisting or GDM, but the risk was notstatistically significant. Unfortunately, blood glucose levels were notmeasured in our study and because our interview was conducted ata mean gestational age of 31.25.6 weeks, it is possible that ourinterview was conducted before some women were diagnosed withgestational diabetes. Other studies have found that women with

gestational diabetes who maintained good metabolic control ofglucose levels throughout pregnancy were at no greater risk fordeliveringa large for gestational age infant than women withoutdiabetes.30 It is possible that had we tested for blood glucose levels,

we would have found excess risk among Latinas with poorlycontrolled diabetes. On the basis of the timing of our interview, it isalso possible that our interview was conducted before some women

were diagnosed with gestational hypertension and preeclampsia,a risk factor for lower birth weight infants that may haveinfluenced our results.

A unique aspect of our study was the inclusion of nutritional

variables in relation to odds of macrosomic birth. Few previous

Table 3 Adjusted logistic regression for risk of infant macrosomia among 348Latina women, San Francisco, CA, 19971999a

Maternal variables Odds ratio

(95% CI)b

Increasing maternal age (10-year increments) 2.59 (1.285.24)

History of diabetes mellitus or gestational diabetes mellitus

with this pregnancy

Yes 1.21 (0.29 5.03)

No 1.00

Pre-pregnancy BMI (kg/m2)

Normal weight/underweight (2 1.14 (0.472.76)

Infant variables

Gestational age (weeks)

40 2.16 (0.954.89)

Infant sex

Male 1.00c

Female 0.42 (0.190.93)

Abbreviation: BMI, body mass index; CI, confidence interval.aFixed model including covariates that were significant atP

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studies have assessed the relationship between food consumptionduring pregnancy and risk of macrosomia among women recruited

without reference to a specific health care need. One French studyof women with gestational diabetes undergoing intensive prenatal

care management reported that higher carbohydrate intake wasassociated with a decreased incidence of macrosomia,31 but ourunderstanding of favorable diets and macronutrient balance innondiabetic women is very limited. Previous studies in multiethnicsamples have found that diabetic, overweight and obese Latina

women are more likely todeliver macrosomic infants than Whitesor African Americans,17,18 and we hypothesize that ethnic-specificenvironmental or behavioral risk factors, such as diet, in additionto metabolic factors, could explain the elevated risk for macrosomicbirth among at-risk Latinas.17,18 In addition, as the rate ofmacrosomic birth was higher in our cohort than the national rateamong Latinas, it is possible that behavioral and/or environmental

factors could also increase the risk of macrosomic birth amonghealthy Latina women.

In unadjusted analyses, we found higher rates of macrosomicinfants among women who consumed less fresh fruit (14.4 versus9.6%), which contrasts with studies showing an associationbetweenhigh maternal serum vitamin C levels and high birth

weight.32 Our group of Latina women reported a high frequency offresh fruit consumption (72% reported eating fresh fruit every dayor two times a day during pregnancy), which is consis tent withother studies on the diets of immigrant Latina women.33

Acculturation in Latinos has beenshown to be associated with

lower fruit and vegetable intakes.

33

In our study, the rate ofmacrosomic birth was lower in women who were taking ironsupplements during pregnancy (3.6 versus 12.4%). As higheriron levels in pregnancy are associated with heavier infant birth

weight,34 it is possible that not taking iron pills in pregnancyis a marker of adequate iron serum levels. In our study of Latina

women, we did not find an association for soda consumption andmacrosomia even though soda is a known risk factor for obesity,35

nor among women who consumed more American food(defined as spaghetti, potatoes and fast foods) a proxy for foods

with a higher glycemic index. In fact, although not statisticallysignificant, we found that macrosomic birth was associated with

lower levels of consumption of American food and sodas duringpregnancy, which may be associated with the reduced riskof macrosomia we found with acculturation (as indicated byself-identification and language use). Further study is neededto identify advantageous and disadvantageous nutritional practicesamong pregnant Latina women.

Additional study, with larger samples, is needed to assess andidentify risk factors for macrosomia in Latina women. The mostimportant limitation of our study was lack of statistical power.

As the study was designed to test alternative hypotheses, we wereunable to fully evaluate the relationships between all study

variables and risk of macrosomia. We could not adequately test

the effect of pre-pregnancy BMI, but with a high prevalence ofoverweight and obesity among Latinas, it is critical to understandthe effect of maternal body mass on perinatal outcomes.Furthermore, if specific dietary components are identified as risks

or protective factors for macrosomic births in Latinas, thisinformation can be used to develop interventions to optimizematernal and infant health outcomes. In addition, if subsequentstudies confirm the excess risk of macrosomia associated witholder Latina women, then health care providers can alert Latinas oftheir increased risk for macrosomia associated with advancedmaternal age. Given the high prevalence of pediatric overweightin Latinos, further studies are needed to ascertain risk factors formacrosomia, as macrosomia is an important precursor to pediatricoverweight.

Acknowledgments

This study was supported by grants to Dr Fuentes-Afflick from the National Center

for Research Resources through a Minority Clinical Associate Physician award

(3 M01 RR0083-34S1), a Generalist Physician Faculty Scholar Award from the

Robert Wood Johnson Foundation and the National Institutes for Child Health and

Human Development (HD 01303). The study interviews were conducted in the

General Clinical Research Center at San Francisco General Hospital and were

partially supported by grant M01 RR00083-41. Dr Heyman is supported by NIH

grant DK 060617.

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