ARTICLE

Prenatal Diet and Child Growth at 18 MonthsJodie M. Dodd, MD, PhD, a, b Jennie Louise, PhD, a, c Andrea R. Deussen, BHSc(Hon), a Andrew J. McPhee, MD, d Julie A. Owens, PhD, a Jeffrey S. Robinson, MDa

OBJECTIVE: Our objective was to evaluate the effect of an antenatal dietary and lifestyle intervention in pregnant women who are overweight or obese on child outcomes at age 18 months.METHODS: We conducted a follow-up study of children at 18 months of age who were born to women who participated in the Limiting Weight Gain in Overweight and Obese Women during Pregnancy to Improve Health Outcomes randomized trial. The primary follow-up study outcome was prevalence of child BMI z scores >85th percentile. Secondary study outcomes included a range of anthropometric measures, neurodevelopment, general health, and child feeding. Intention to treat principles were used in analyses, according to the treatment group allocated at randomization. RESULTS: A total of 1602 children were assessed at age 18 months (lifestyle advice, n = 816; standard care, n = 786), representing 75.0% of the eligible sample (n = 2136). There were no statistically significant differences in the prevalence of child BMI z scores >85th percentile for children born to women in the lifestyle advice group, compared with the standard care group (lifestyle advice, 505 [47.11%] versus standard care, 483 [45.36%]; adjusted relative risk: 1.04; 95% confidence interval: 0.94 to 1.16; P = .45). There was no evidence of effects on child growth, adiposity, neurodevelopment, or dietary and physical activity patterns.CONCLUSIONS: There is no evidence that providing pregnant women who were overweight or obese with an antenatal dietary and lifestyle intervention altered 18-month child growth and adiposity.

abstract

aDiscipline of Obstetrics and Gynaecology, Robinson Research Institute and cAdelaide Health Technology Assessment, School of Public Health, University of Adelaide, Adelaide, Australia; and Departments of bWomen’s and Babies Division, Perinatal Medicine and dNeonatal Medicine, Women’s and Children’s Hospital, Adelaide, Australia

Dr Dodd conceptualized and designed the study, designed the data collection instruments, coordinated and supervised data collection, provided initial data interpretation, and drafted the initial manuscript; Drs Owens and Robinson conceptualized and designed the study; Dr McPhee conceptualized and designed the study and designed the data collection instruments; Ms Deussen designed the data collection instruments and coordinated and supervised data collection; Dr Louise planned and completed the analyses and provided the initial data interpretation; and all authors reviewed and critically revised the manuscript for important intellectual content, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work.

This trial has been registered with the Australian and New Zealand Clinical Trials Registry (http:// anzctr. org. au) (identifier ACTRN12607000161426).

DOI: https:// doi. org/ 10. 1542/ peds. 2018- 0035

Accepted for publication Jun 14, 2018

PEDIATRICS Volume 142, number 3, September 2018:e20180035

WHAT’S KNOWN ON THIS SUBJECT: Maternal obesity is associated with an increased risk of pre-school obesity in the child. In tackling childhood obesity, the World Health Organization has recognized the need to integrate recommendations and health care interventions for women before conception and during pregnancy.

WHAT THIS STUDY ADDS: There was no effect of an antenatal dietary intervention on child growth or adiposity at 18 months of age. We identified a significant rate of overweight and obesity in early childhood and high prevalence of at-risk obesogenic behaviors.

To cite: Dodd JM, Louise J, Deussen AR, et al. Prenatal Diet and Child Growth at 18 Months. Pediatrics. 2018;142(3): e20180035

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The World Health Organization (WHO) estimates 42 million children younger than the age of 5 years are overweight or obese globally, 1 representing a significant burden of disease and associated health care costs.2 Early-life exposures contribute to an individual child’s risk of obesity, including parental obesity, infant birth weight and early growth, sleep duration, feeding practices, and sedentary activity or screen time.3 Maternal obesity is associated with an increased risk of pre-school obesity, with the risk ranging from a 1.6-fold4 to a more than sixfold increase5 compared with offspring of women of normal BMI, potentially creating a vicious cycle impacting successive generations.6

In tackling childhood obesity, WHO acknowledges the need for complementary strategies, including integration of health care interventions for women during pregnancy.7 Much research has been focused on antenatal interventions to limit gestational weight gain (GWG), 8 with findings from an individual participant data meta-analysis involving more than 12 000 women across 36 randomized studies indicating a modest 0.7 kg reduction in GWG.8 However, most researchers have reported outcomes to birth only, 8 with little attention to ongoing follow-up and impact on longer-term outcomes, including childhood obesity.

We have reported previously the effect of an antenatal intervention in women who are overweight or obese in significantly improving diet and physical activity9 and reducing the risk of infant birth weight >4 and 4.5 kg.10, 11 In this article, we report the effect of the LIMIT antenatal dietary and lifestyle intervention on 18-month child outcomes.

METHODS

The LIMIT (Limiting Weight Gain in Overweight and Obese Women

During Pregnancy to Improve Health Outcomes) randomized trial was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426), and the methods and clinical findings have been reported previously9 – 11 and are detailed in the Supplemental Information. Women with a singleton pregnancy, between 10 and 20 weeks’ gestation, and a BMI ≥25.0 were recruited and randomly selected to receive an antenatal dietary and lifestyle intervention (lifestyle advice) or standard antenatal care (standard care).10

Women randomly assigned to lifestyle advice received an intervention across pregnancy involving a combination of dietary, exercise, and behavioral strategies and goal setting, provided by a research dietician and trained research assistants.9, 10 Dietary and physical activity information was consistent with Australian standards.12, 13

We conducted follow-ups of children born to women who participated in the LIMIT randomized trial 18 months after birth (Supplemental Information). After ethics approval and after obtaining informed parental consent, a trained research assistant conducted each child assessment while blinded to the treatment group allocated at trial entry. The primary outcome was child BMI z score >85th percentile for age and sex.14

A range of secondary outcomes included the following:

1. Child anthropometry: by using an established and validated protocol, 15, 16 child length, weight, weight-for-length, and anthropometric measures (arm, thigh, waist and hip circumferences; biceps, triceps, subscapular, abdominal, suprailiac, and thigh skinfold thickness measures [SFTMs]) were obtained. Measurement of child skinfold thickness17, 18

is considered a reliable and relatively noninvasive method of assessing fat distribution, having been correlated with more invasive measures.17, 19 – 21 Furthermore, percentage fat as determined by SFTMs has been validated against dual-energy x-ray absorptiometry calculations of fat mass in both infants and children.17, 22 Weight, length, BMI, weight-for-length, and head circumference measures were converted to z scores for age and sex by using WHO standards14, 23;

2. Child neurodevelopment: the Ages and Stages Questionnaire (ASQ) completed by the child’s primary caregiver was used to assess neurodevelopment across 5 domains, reflecting communication, gross motor, fine motor, problem solving, and personal-social skills.24 Children with a score in any domain >2 SD below the mean were referred for medical assessment;

3. Child dietary intake, physical activity and sedentary behavior, and sleep patterns were assessed via questionnaire on the basis of Growing Up in Australia: the Longitudinal Study of Australian Children25 and included duration of breast or formula feeding; introduction of solid foods; the number of servings of fruits, vegetables, and milk consumed daily; the consumption of red meat and processed meats per week; and consumption of noncore foods, including salty snacks, fried potatoes, takeaway foods, soft drinks, and other “extra” foods.25 Caregivers were asked to estimate the hours per week spent playing outdoors, screen time and other sedentary behaviors, duration of overnight sleeping, and daytime sleeping25; and

4. Family food behaviors included whether family meals were eaten together, preparation of different meals for children, use of food to

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encourage behaviors, and use of a bottle at bedtime.25

Sample Size

The available sample size at 18 months was predetermined by the LIMIT trial, with 2212 women randomly selected.10 We anticipated an incidence in the standard care group of BMI z scores >85th percentile of 25%.26 A sample of 1350 children (75% follow-up) provided 80% power to detect a difference in incidence of BMI z scores >85th percentile of 6.4% and small but relevant differences of 0.15 to 0.16 SD in continuous outcomes.

Statistical Analysis

Data were analyzed by using intention to treat principles according to the treatment group the woman was randomly assigned to in pregnancy. Missing data were imputed by using the fully conditional specification (chained equations) method to create 100 complete data sets under the assumption that the data were missing at random. To make the missing-at-random assumption more plausible, a range of auxiliary variables, including maternal baseline and infant birth and 6-month follow-up measures (Supplemental Information, Supplemental Tables 7–10), were included in the imputation model. The results of imputed analyses were compared with those from complete-case analyses, and further sensitivity analyses were conducted for the primary outcome on the assumption that data were missing not at random, assuming both higher and lower incidence of z scores >85th percentile compared with observed data, in both or only 1 treatment group. Imputed outcomes included anthropometric measures, SFTMs, and Ages and Stages scores. No data were available to enable meaningful imputation of missing dietary and physical activity values.

Adjusted and unadjusted analyses were performed, with adjustment for stratification variables (maternal early-pregnancy BMI [25.0–29.9 vs ≥30.0], parity [0 vs ≥1], and center of birth), maternal socioeconomic status (Socioeconomic Indexes for Areas [SEIFA] Index of Relative Socio-Economic Disadvantage [IRSD] quintile27), age, and smoking status. Child outcomes other than z scores were additionally adjusted for sex and actual age at assessment. For binary outcomes, relative risks with 95% confidence intervals (CIs) were estimated by using log binomial regression. For continuous outcomes, differences in means with 95% CI were estimated by using linear regression. Secondary analyses were performed to test for effect modification by maternal BMI category measured at the women’s first prenatal visit. Statistical significance was set at P < .05 (2-sided) with no adjustment for multiple comparisons. All analyses followed a prespecified plan.

RESULTS

There were 2136 live-born infants from the LIMIT randomized trial contributing data to the imputed analyses (Fig 1). In total, 1602 children (lifestyle advice, n = 816; standard care, n = 786) (representing 75.0% of the eligible sample) were assessed at 18 months. Baseline characteristics of eligible maternal participants (Table 1) were similar to the entire randomly assigned cohort and similar between treatment groups.10

The prevalence of child BMI z scores >85th percentile was not significantly different between treatment groups (lifestyle advice, 505 [47.11%] versus standard care, 483 [45.36%]; adjusted relative risk [aRR]: 1.04; 95% CI: 0.94 to 1.16; P = .45) and similarly for child BMI z scores >90th percentile (lifestyle advice, 407 [37.97%] versus standard care, 394

[37.01%]; aRR: 1.02; 95% CI: 0.90 to 1.15; P = .78) (Table 2). There were no statistically significant differences in child weight (lifestyle advice, 11.90 kg [±1.55] versus standard care 11.93 kg [±1.55]; adjusted mean difference [aMD]: −0.00; 95% CI: −0.14 to 0.13; P = .96), weight z score (lifestyle advice, 0.73 [±0.98] versus standard care, 0.74 [±0.99]; aMD: −0.02; 95% CI: −0.11 to 0.08; P = .73), length (lifestyle advice, 82.90 cm [±4.38] versus standard care, 83.06 cm [±4.25]; aMD: −0.05; 95% CI: −0.40 to 0.30; P = .79), length z score (lifestyle advice, 0.10 [±1.26] versus standard care, 0.16 [±1.20]; aMD: −0.05; 95% CI: −0.17 to 0.07; P = .43), weight-for-length ratio (lifestyle advice, 0.14 [±0.01] versus standard care, 0.14 [±0.01]; aMD: −0.00; 95% CI: −0.00 to 0.00; P = .66), or weight-for-length ratio z score (lifestyle advice, 0.92 [±1.13] versus standard care, 0.89 [±1.04]; aMD: 0.02; 95% CI: −0.09 to 0.13; P = .74). Abdominal circumference was statistically significantly greater among children born to women who received lifestyle advice (lifestyle advice, 48.92 cm [±3.81] versus standard care, 48.43 cm [±3.46]; aMD: 0.49; 95% CI: 0.12 to 0.85; P = .009), although the remaining body circumference measures did not differ.

Subscapular SFTM (lifestyle advice, 6.77 mm [±1.86] versus standard care, 6.50 mm [±1.67]; aMD: 0.24; 95% CI: 0.03 to 0.46; P = .025) and sum of SFTMs (lifestyle advice, 55.96 mm [±12.65] versus standard care, 54.11 mm [±11.77]; aMD: 1.68; 95% CI: 0.12 to 3.24; P = .035) were statistically significantly greater among children born to women who received lifestyle advice (Table 3), although the remaining SFTMs did not differ.

Child Ages and Stages total scores were not statistically significantly different between the treatment groups (lifestyle advice, 250.48 [±36.41] versus standard care, 247.64 [±37.60]; aMD: 2.70; 95% CI:

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−1.26 to 6.66; P = .18) (Table 4). Individual components of the Ages and Stages score did not differ significantly between the 2 groups (Table 4).

At 18 months, dietary patterns were similar, with ∼90% of children having ever been breastfed (lifestyle advice, 627 [90.48%] versus standard care, 591 [90.64%]; aRR: 1.01; 95% CI: 0.97 to 1.05; P = .69) and with the mean duration of breastfeeding being ∼8 months (lifestyle advice, 8.28 [±6.01] versus standard care, 8.69 [±6.10]; aMD: −0.26; 95% CI: −0.92 to 0.40; P = .44) (Table 5). There were no statistically significant differences in the number of servings per day of fruit (lifestyle advice, 1.94 [±0.99] versus standard care, 1.95

[±0.95]; aMD: −0.01; 95% CI: −0.11 to 0.10; P = .89), vegetables (lifestyle advice, 1.72 [±0.95] versus standard care, 1.66 [± 0.94]; aMD: 0.07; 95% CI: −0.03 to 0.17; P = .18), or milk (lifestyle advice, 2.18 [± 1.10] versus standard care, 2.14 [± 1.17]; aMD: 0.06; 95% CI: −0.06 to 0.18; P = .35). There were no statistically significant differences between the groups in consumption of red (lifestyle advice, 3.62 [± 3.26] versus standard care, 3.53 [± 3.18]; aMD: 0.09; 95% CI: −0.25 to 0.43; P = .59) or processed meat (lifestyle advice, 2.37 [± 2.65] versus standard care, 2.40 [± 2.87]; aMD: −0.06; 95% CI: −0.35 to 0.24; P = .71). Similarly, consumption of extras, salty snacks, and soft drinks

did not differ significantly between the groups.

Reported time per week engaged in physical activity outdoors (lifestyle advice, 16.24 hours [±10.16] versus standard care, 15.73 hours [± 9.78]; aMD: 0.50; 95% CI: −0.58 to 1.57; P = .37) and screen time (lifestyle advice, 15.29 hours [±13.40] versus standard care, 15.12 hours [± 13.81]; aMD: −0.04; 95% CI: −1.50 to 1.43; P = .96) did not significantly differ between the 2 groups (Table 6). The mean duration of sleep overnight was ∼11 hours (lifestyle advice, 10.98 hours [± 1.03] versus standard care, 10.98 hours [± 1.00]; aMD: 0.00; 95% CI: −0.11 to 0.11; P = .93), with no differences identified in the proportion of children having >1 daytime sleep (lifestyle advice, 115 [16.59%] versus standard care, 110 [16.92%]; aRR: 0.99; 95% CI: 0.78 to 1.25; P = .91).

Women and children from the lifestyle advice group were significantly less likely than those in the standard care group to have family meals together most of the time (lifestyle advice, 533 [77.02%] versus standard care, 534 [82.03%]; aRR: 0.93; 95% CI: 0.88 to 0.98; P = .01) or for all members of the family to eat the same food on most occasions (lifestyle advice, 517 [74.60%] versus standard care, 520 [79.75%]; aRR: 0.94; 95% CI: 0.89 to 0.99; P = .03). There were no significant differences in using food to encourage behavior (lifestyle advice, 204 [29.78%] versus standard care, 184 [28.31%]; aRR: 1.05; 95% CI: 0.90 to 1.24; P = .52). Few parents of children with BMIs >85th percentile perceived their child to be overweight (lifestyle advice, 7 [2.30%] versus standard care, 8 [2.95%]).

There was no evidence that the effect of the antenatal intervention was modified by maternal early-pregnancy BMI category for any of the reported outcomes (data not shown).

DODD et al4

FIGURE 1Flow of participants.

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DISCUSSION

In our findings, it was indicated that providing an antenatal dietary and lifestyle intervention for women who were overweight or obese was not associated with effects on child growth, adiposity, neurodevelopment, or diet and related behaviors at 18 months. The statistically significant differences in abdominal circumference, subscapular SFTM, and the sum of SFTMs were likely due to chance, particularly as the actual differences were small and unlikely to be clinically relevant.

We have conducted the largest randomized trial to date in which an antenatal dietary and lifestyle intervention in women who were overweight and obese was evaluated, the findings representing the largest, most extensive and complete follow-up of children to

18 months. Our methodology was robust, with accurate measurement of early pregnancy weight, height, and BMI; detailed maternal dietary and physical activity history; and consistent provision of the intervention to participants. In our follow-up, we adhered to a research-quality protocol with standardized assessment of anthropometric measures and consistent evaluation of dietary and physical activity, sedentary behavior, and sleep patterns, all of which are well-recognized early-life factors contributing to child overweight and obesity.3

Although only 75% of the available cohort was assessed and contributed data at 18 months, the baseline and clinical characteristics of women and children for whom data were available and who participated in the follow-up study were similar

between the 2 randomly assigned treatment groups and were similar to the full randomly assigned cohort.10 Furthermore, in our analyses, we included all children eligible for 18-month follow-up (96.6% of those randomly selected) through multiple imputation to address missing data. Additionally, in our sensitivity analyses, we used data imputed under a range of missing-not-at-random scenarios and demonstrated that results remained consistent under various plausible assumptions about the magnitude and direction of the difference between missing and observed data. We therefore consider the risk of bias and any impact on the validity of our findings to be low.

We found no evidence of effect from a comprehensive dietary and lifestyle intervention provided during pregnancy for women who are overweight or obese on measures

PEDIATRICS Volume 142, number 3, September 2018 5

TABLE 1 Baseline Maternal Characteristics From Children Assessed at 18 Months of Age

Characteristic Lifestyle Advice Standard Care Overall

n = 816 n = 786 N = 1602

Maternal age in y at trial entry, mean (SD) 29.73 (5.42) 29.98 (5.33) 29.85 (5.38)Gestational age in wk at trial entry, median

(interquartile range)14.29 (12.00–17.00) 14.29 (12.00–17.14) 14.29 (12.00–17.14)

BMI at trial entry, median (interquartile range) 31.05 (27.90–35.90) 30.90 (27.50–35.50) 31.00 (27.80–35.80)BMI category, n (%) 25.0–29.9 338 (41.42) 341 (43.38) 679 (42.38) 30.0–34.9 240 (29.41) 226 (28.75) 466 (29.09) 35.0–39.9 149 (18.26) 127 (16.16) 276 (17.23) ≥40.0 89 (10.91) 92 (11.70) 181 (11.30)Public patient, n (%) 798 (97.79) 769 (97.84) 1567 (97.82)Wt in kg at trial entry, mean (SD) 88.53 (17.19) 87.95 (17.61) 88.25 (17.39)Height in cm at trial entry, mean (SD) 164.79 (6.54) 164.80 (6.50) 164.80 (6.52)Ethnicity, n (%) White 740 (90.69) 714 (90.84) 1454 (90.76) Indian 34 (4.17) 26 (3.31) 60 (3.75) Asian 19 (2.33) 28 (3.56) 47 (2.93) Other 23 (2.83) 18 (2.29) 41 (2.56)Smoking, n (%) 87 (10.66) 75 (9.54) 162 (10.11)SEIFA IRSD quintile, n (%)a

1 244 (29.90) 215 (27.35) 459 (28.65) 2 193 (23.65) 197 (25.06) 390 (24.34) 3 137 (16.79) 115 (14.63) 252 (15.73) 4 110 (13.48) 133 (16.92) 243 (15.17) 5 131 (16.05) 125 (15.90) 256 (15.98)Infant sex Male 401 (49.14) 400 (50.89) 801 (50.00) Female 415 (50.86) 386 (49.11) 801 (50.00)Age in mo at assessment, median (interquartile

range)18.64 (17.52–21.12) 18.78 (17.49–21.02) 18.71 (17.52–21.09)

a Socioeconomic index as measured by SEIFA IRSD.

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of child growth, adiposity, and neurodevelopment at 18 months. This is in contrast to our primary trial reports in which significant, albeit modest, changes in maternal

diet and physical activity during pregnancy9 were associated with an 18% and 41% relative reduction in risk of infant birth weight >410 and 4.5 kg, respectively.11 Although this

may indeed be reflective of a true lack of any persisting effect from modifications in maternal diet and birth weight on weight at 18 months, it may also indicate that other factors

DODD et al6

TABLE 2 Eighteen-Month Child Weight and Anthropometric Outcomes by Treatment Group

Outcome Lifestyle Advice, n = 1071

Standard Care, n = 1065

Unadjusted Estimate (95% CI)

Unadjusted P Adjusted Estimate (95% CI) Adjusted P

BMI z score >85th percentile, n (%)a

505 (47.11) 483 (45.36) 1.04 (0.93 to 1.16) .486 1.04 (0.94 to 1.16) .454

Wt in kg, mean (SD) 11.90 (1.55) 11.93 (1.55) −0.02 (−0.17 to 0.13) .748 −0.00 (−0.14 to 0.13) .959Wt z score, mean (SD) 0.73 (0.98) 0.74 (0.99) −0.01 (−0.11 to 0.08) .822 −0.02 (−0.11 to 0.08) .734Length in cm, mean (SD) 82.90 (4.38) 83.06 (4.25) −0.17 (−0.60 to 0.27) .450 −0.05 (−0.40 to 0.30) .788

Length z score, mean (SD) 0.10 (1.26) 0.16 (1.20) −0.05 (−0.17 to 0.07) .385 −0.05 (−0.17 to 0.07) .425Wt-for-length, mean (SD) 0.14 (0.01) 0.14 (0.01) 0.00 (−0.00 to 0.00) .734 0.00 (−0.00 to 0.00) .662Wt-for-length z score,

mean (SD)0.92 (1.13) 0.89 (1.04) 0.03 (−0.08 to 0.14) .610 0.02 (−0.09 to 0.13) .744

BMI, mean (SD) 17.33 (1.75) 17.25 (1.57) 0.07 (−0.09 to 0.23) .364 0.06 (−0.10 to 0.21) .480BMI z score, mean (SD) 0.96 (1.17) 0.92 (1.06) 0.04 (−0.07 to 0.15) .434 0.03 (−0.07 to 0.14) .547Head circumference in

cm, mean (SD)47.98 (1.66) 48.05 (1.62) −0.08 (−0.24 to 0.08) .338 −0.04 (−0.19 to 0.10) .581

Head circumference z score, mean (SD)

0.74 (1.06) 0.79 (1.06) −0.05 (−0.15 to 0.06) .367 −0.04 (−0.15 to 0.06) .410

Chest circumference in cm, mean (SD)

49.47 (2.59) 49.27 (2.60) 0.21 (−0.06 to 0.48) .135 0.22 (−0.04 to 0.49) .095

Abdomen circumference in cm, mean (SD)

48.92 (3.81) 48.43 (3.46) 0.49 (0.12 to 0.85) .009 0.49 (0.12 to 0.85) .009

Arm circumference in cm, mean (SD)

16.01 (1.27) 15.95 (1.23) 0.06 (−0.07 to 0.19) .337 0.06 (−0.06 to 0.19) .332

Bio-impedance R0 (Ω), mean (SD)b

728.12 (90.27) 735.53 (76.01) −7.41 (−18.84 to 4.02) .203 −7.73 (−19.01 to 3.56) .179

BMI z score >90th percentile, n (%)a

407 (37.97) 394 (37.01) 1.03 (0.90 to 1.16) .694 1.02 (0.90 to 1.15) .779

Wt z score >85th percentile, n (%)a

424 (39.63) 406 (38.15) 1.04 (0.92 to 1.17) .532 1.03 (0.91 to 1.16) .621

Wt z score >90th percentile, n (%)a

306 (28.59) 316 (29.69) 0.96 (0.83 to 1.12) .624 0.96 (0.82 to 1.11) .576

WFL z score >85th percentile, n (%)a

501 (46.80) 475 (44.60) 1.05 (0.94 to 1.17) .378 1.04 (0.94 to 1.16) .436

WFL z score >90th percentile, n (%)a

388 (36.24) 385 (36.11) 1.00 (0.88 to 1.14) .956 1.00 (0.88 to 1.13) .998

Values for continuous outcomes are mean and SD, and treatment effects are differences in means. Adjusted analyses included the stratification variables BMI category, parity, and center, as well as maternal age, socioeconomic status, and maternal smoking. Non–z score outcomes were additionally adjusted for actual age at assessment and infant sex.a Values for binary outcomes are number and percentage, and treatment effects are relative risks. All estimates are based on imputed data including all infants who were eligible for the follow-up study.b R0 = resistance at current frequency of 0 KHz

TABLE 3 Eighteen-Month Child SFTMs by Treatment Group

Outcome, mm Lifestyle Advice (n = 1071), mean (SD)

Standard Care (n = 1065), mean (SD)

Unadjusted Estimate (95% CI)

Unadjusted P Adjusted Estimate (95% CI) Adjusted P

Biceps SFTM 6.70 (2.04) 6.50 (1.93) 0.19 (−0.04 to 0.43) .106 0.18 (−0.06 to 0.41) .138Triceps SFTM 10.68 (2.74) 10.45 (2.74) 0.24 (−0.08 to 0.56) .148 0.23 (−0.09 to 0.55) .160Subscapular SFTM 6.77 (1.86) 6.50 (1.67) 0.27 (0.05 to 0.48) .016 0.24 (0.03 to 0.46) .025Suprailiac SFTM 8.10 (2.85) 8.12 (2.94) −0.02 (−0.37 to 0.34) .931 −0.05 (−0.40 to 0.31) .798Abdomen SFTM 7.42 (2.47) 7.26 (2.33) 0.16 (−0.13 to 0.45) .278 0.13 (−0.16 to 0.41) .379Thigh SFTM 15.83 (4.10) 15.48 (3.54) 0.35 (−0.12 to 0.81) .140 0.29 (−0.16 to 0.75) .203Sum of SFTMs 55.96 (12.65) 54.11 (11.77) 1.85 (0.27 to 3.43) .022 1.68 (0.12 to 3.24) .035

Values for continuous outcomes are mean and SD, and treatment effects are differences in means. All estimates are based on imputed data including all infants who were eligible for the follow-up study. Adjusted analyses included the stratification variables BMI category, parity, and center, as well as maternal age, socioeconomic status, and maternal smoking. Non–z score outcomes were additionally adjusted for actual age at assessment and infant sex.

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are of relatively greater importance in driving early ex-utero growth and development, particularly in a high-risk cohort of children in which the prevalence of BMI z scores >85th percentile was >45%.

We are aware of 2 randomized trials in which an antenatal dietary and lifestyle intervention has been provided28, 29 and subsequent follow-up of children at ∼2 years of age has occurred.30 – 34 Tanvig et al30, 31 conducted follow-up of children whose mothers participated in the Danish Life in Pregnancy randomized trial, 28 reporting data for 150 children aged between 2.5 and 3.2 years, representing 42% of the randomly assigned cohort. There were no significant differences identified between intervention and control group children with regards to BMI, 30, 31 metabolic risk factors, 30 or child anthropometric measures, including body circumferences and SFTMs as well as body composition determined by dual energy radiograph.31 These findings

are broadly consistent with ours, although the incidence of overweight and obesity in this cohort of children was ∼9%, 30, 31 far lower than the 45% observed in our trial population at 18 months.

In the ROLO (randomized controlled trial of low glycemic index diet in pregnancy to prevent macrosomia) trial, researchers evaluated the effect of a low glycemic index diet in women at risk for infant macrosomia, recruiting women who had previously given birth to an infant with weight >4 kg, although not all women were overweight or obese (mean BMI, 26.8).29 Follow-up of children at 2 years of age was conducted in 35% of the eligible cohort.32 – 34 Although no specific data relating to between-group comparisons are presented, child anthropometric measures did not differ between the intervention and control groups.33

Our cohort of 18-month-old children is one at considerable risk, with

high rates of overweight and obesity already evident, in addition to many high-risk obesogenic behaviors. Many participants did not meet the daily dietary recommendations for a child aged 0 to 2 years, 35 consuming more than the recommended 1 serving of fruit (93%) and less than the recommended 2.5 servings of vegetables (48.8%) per day. Furthermore, children consumed both red and processed meats and extra foods ∼6 times per week, with additional high consumption of salty snacks and soft drinks. These dietary intakes far exceed the recommendations to limit consumption of such discretionary foods to less than once per week.35 In available survey data from the Australian Bureau of Statistics, it is suggested that children aged 2 to 18 years have similarly poor consumption of fruits and vegetables, with <1% meeting the daily recommended vegetable intake, although 31% met the recommended intake of fruit.36 Low consumption of fruit and vegetables37 and high

PEDIATRICS Volume 142, number 3, September 2018 7

TABLE 4 Eighteen-Month Child Neurodevelopmental Outcomes by Treatment Group Assessed by Using the ASQ

Outcome Lifestyle Advice, n = 1071

Standard Care, n = 1065

Unadjusted Estimate (95% CI)

Unadjusted P Adjusted Estimate (95% CI) Adjusted P

Ages and Stages communication score, mean (SD)

44.79 (13.86) 44.14 (14.44) 0.65 (−0.93 to 2.23) .421 0.58 (−0.97 to 2.12) .464

Ages and Stages gross motor score, mean (SD)

56.64 (8.43) 56.22 (8.60) 0.41 (−0.55 to 1.38) .400 0.41 (−0.55 to 1.38) .398

Ages and Stages fine motor score, mean (SD)

53.30 (8.36) 53.28 (8.10) 0.01 (−0.87 to 0.90) .979 0.06 (−0.82 to 0.93) .898

Ages and Stages problem solving score, mean (SD)

45.57 (11.56) 44.87 (11.59) 0.70 (−0.58 to 1.99) .283 0.69 (−0.59 to 1.96) .290

Ages and Stages personal social score, mean (SD)

50.02 (9.22) 49.19 (9.46) 0.83 (−0.25 to 1.90) .130 0.75 (−0.32 to 1.82) .171

Ages and Stages total score, mean (SD)

250.48 (36.41) 247.64 (37.60) 2.84 (−1.18 to 6.86) .166 2.70 (−1.26 to 6.66) .181

Ages and Stages ≥2 below cutoff, n (%)a

16 (1.51) 21 (1.98) 0.77 (0.38 to 1.53) .451 0.77 (0.38 to 1.53) .451

Adjusted analyses included the stratification variables BMI category, parity, and center. Outcomes were additionally adjusted for maternal age, socioeconomic status, maternal smoking, and actual age at assessment. Values are mean and SD (or number and percentage), and treatment effects are differences in means (or relative risks) and are based on imputed data including all infants who were eligible for the follow-up study. Outcomes presented as mean (SD) have effect estimates presented as mean difference; outcomes presented as n (%) have effect estimates as relative risk.a Adjusted model was analyzed by using log Poisson regression with robust variance estimation because of convergence issues with log binomial model.

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consumption of discretionary foods, 37 including soft drinks, 38 from an early age contribute to the establishment of suboptimal eating habits that persist into adolescence.37

Although physical activity in young children can be difficult to quantify, current recommendations advise a minimum of 3 hours of physical activity each day for children aged

1 to 3 years, with no screen time for children <2 years.39 Participants in our study did not meet recommendations for outdoor play, spending on average 2.3 hours per day, but well exceeded

DODD et al8

TABLE 5 Eighteen-Month Child Dietary Patterns

Outcome Lifestyle Advice, n = 693

Standard Care, n = 652

Unadjusted Estimate (95% CI)

Unadjusted P Adjusted Estimate (95% CI) Adjusted

Ever breastfed, n (%)

627 out of 693 (90.48)

591 out of 652 (90.64)

1.00 (0.96 to 1.03) .916 1.01 (0.97 to 1.05) .687

Duration of breastfeeding in mo, mean (SD)

8.28 (6.01) 8.69 (6.10) −0.41 (−1.10 to 0.27) .238 −0.26 (−0.92 to 0.40) .437

Servings of fruit per d, mean (SD)

1.94 (0.99) 1.95 (0.95) −0.02 (−0.12 to 0.09) .749 −0.01 (−0.11 to 0.10) .887

Consume <1 serving fruit per d, n (%)

47 out of 691 (6.80) 45 out of 648 (6.94) 0.98 (0.66 to 1.45) .918 0.98 (0.66 to 1.45) .911

Servings of vegetables per d, mean (SD)

1.72 (0.95) 1.66 (0.94) 0.06 (−0.04 to 0.17) .215 0.07 (−0.03 to 0.17) .176

Consume <2 serving vegetables per d, n (%)

330 out of 690 (47.83)

322 out of 646 (49.85)

0.96 (0.86 to 1.07) .460 0.95 (0.85 to 1.07) .402

Cups of milk per d, mean (SD)

2.18 (1.10) 2.14 (1.17) 0.05 (−0.07 to 0.17) .432 0.06 (−0.06 to 0.18) .346

Consume <1 cup milk per d, n (%)

55 out of 677 (8.12) 63 out of 639 (9.86) 0.82 (0.58 to 1.16) .272 0.80 (0.56 to 1.13) .205

Servings of red meat per wk, mean (SD)

3.62 (3.26) 3.53 (3.18) 0.08 (−0.26 to 0.43) .634 0.09 (−0.25 to 0.43) .594

Consume red meat <3 times per wk, n (%)

249 out of 690 (36.09)

243 out of 649 (37.44)

0.96 (0.84 to 1.11) .607 0.97 (0.84 to 1.11) .631

Servings of processed meat per wk, mean (SD)

2.37 (2.65) 2.40 (2.87) −0.02 (−0.32 to 0.27) .882 −0.06 (−0.35 to 0.24) .709

Consume processed meat >2 times per wk, n (%)

239 out of 689 (34.69)

218 out of 650 (33.54)

1.03 (0.89 to 1.20) .658 1.00 (0.86 to 1.16) .965

Servings of fried potatoes or salty snacks per wk, mean (SD)

1.84 (2.30) 1.83 (2.38) 0.01 (−0.24 to 0.26) .942 −0.03 (−0.28 to 0.21) .794

Consume fried potatoes or salty snacks >1 time per wk, n (%)

414 out of 690 (60.00)

381 out of 652 (58.44)

1.03 (0.94 to 1.12) .560 0.98 (0.91 to 1.07) .667

Servings of extra foods per wk, mean (SD)a

6.11 (6.67) 5.75 (6.55) 0.36 (−0.35 to 1.07) .318 0.24 (−0.47 to 0.94) .510

Consume extra foods >1 time per wk, n (%)a

556 out of 691 (80.46)

516 out of 652 (79.14)

1.02 (0.96 to 1.07) .547 1.01 (0.95 to 1.06) .833

Cups of soft drink per wk, mean (SD)

0.77 (2.69) 0.65 (2.58) 0.11 (−0.17 to 0.40) .426 0.09 (−0.19 to 0.38) .508

Continuous outcomes were analyzed by using linear regression. Adjusted models included as covariates center, parity, BMI category, SEIFA IRSD quintile, smoking, maternal age at consent, infant sex, and actual age at assessment. Adjusted models included as covariates center, parity, BMI category, SEIFA IRSD quintile, smoking, maternal age at consent, infant sex, and actual age at assessment. Binary outcomes were analyzed by using log binomial regression models, with the exception of footnoted outcomes. Values are mean and SD or number and percent, and treatment effects are differences in means (or relative risks). Missing data have not been imputed. Outcomes presented as mean (SD) have effect estimates presented as mean difference; outcomes presented as n (%) have effect estimates as relative risk.a Adjusted analyses were performed by using log Poisson regression with robust variance estimation because of convergence issues with log binomial models.

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screen time recommendations with an average of 2.2 hours per day. Similar findings have been reported by others, 40 with evidence that maternal behaviors are important in both encouraging physical activity and reducing screen time.41

Overweight and obesity are highly prevalent in the general community, often resulting in a perception of “normality.” Despite >45% of children in this follow-up study being overweight or obese, only 2.6% of parents correctly identified this. This is not uncommon, with correct recognition of child overweight and obesity reported to vary between 7.5%42, 43 and 50%.44 Contributing factors include the child’s age and the parent’s own weight.44

CONCLUSIONS

Providing an antenatal dietary and lifestyle intervention for pregnant

women who were overweight and obese did not alter child growth and adiposity at 18 months. Ongoing follow-up of this cohort of children is warranted in view of the well-recognized association between high infant birth weight and subsequent obesity45 and the high rates of overweight, obesity, and obesogenic behaviors evident at such an early age.

ACKNOWLEDGMENTS

We thank the 2212 women who participated in the LIMIT randomized trial and the 1602 parents and infants who contributed to the 18-month outcome data. The following persons in Adelaide, South Australia, participated in the 18-month follow-up of the LIMIT Trial: the coordinating team: J.M. Dodd, A. Deussen, J. Louise, A. Newman, L. Kannieappan, M. Kelsey, C. Sheppard, Z. Sui, N. Salehi, J. Koch,

S. Hendrijanto, D. Post, M. Cooney, A. Webber, R. Bartley, C. Holst, K. Robinson, S. Zhang, and V. Ball; for statistical analyses: J. Louise; and the writing group: J.M. Dodd, J. Louise, A. McPhee, A. Deussen, J.A. Owens, and J.S. Robinson.

PEDIATRICS Volume 142, number 3, September 2018 9

Address correspondence to Jodie M. Dodd, MD, PhD, The University of Adelaide, Women’s and Children’s Hospital, 72 King William Rd, North Adelaide, SA 5006, Australia. E-mail: jodie.dodd@adelaide.edu.au

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2018 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

FUNDING: Supported by intramural funding from the University of Adelaide Discipline of Obstetrics and Gynaecology and the Robinson Research Institute.

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

ABBREVIATIONS

aMD:  adjusted mean differenceaRR:  adjusted relative riskASQ:  Ages and Stages

QuestionnaireCI:  confidence intervalGWG:  gestational weight gainIRSD:  Index of Relative Socio-

Economic DisadvantageSEIFA:  Socioeconomic Indexes

for AreasSFTM:  skinfold thickness

measureWHO:  World Health Organization

TABLE 6 Eighteen-Month Child Physical Activity and Sleep Patterns

Outcome Lifestyle Advice, n = 693

Standard Care, n = 650

Unadjusted Estimate (95% CI)

Unadjusted P Adjusted Estimate (95% CI) Adjusted P

Hours per wk playing outdoors, mean (SD)

16.24 (10.16) 15.73 (9.78) 0.52 (−0.55 to 1.59) .345 0.50 (−0.58 to 1.57) .366

Hours per wk screen time, mean (SD)

15.29 (13.40) 15.12 (13.81) 0.17 (−1.31 to 1.66) .819 −0.04 (−1.50 to 1.43) .962

Duration of overnight sleep in h, mean (SD)

10.98 (1.03) 10.98 (1.00) 0.00 (−0.11 to 0.11) .966 0.00 (−0.11 to 0.11) .934

More than 1 d-time nap, n (%)

115 out of 693 (16.59)

110 out of 650 (16.92)

0.98 (0.77 to 1.24) .872 0.99 (0.78 to 1.25) .906

Binary outcomes were analyzed using log binomial regression models. Adjusted models included as covariates center, parity, BMI category, SEIFA IRSD quintile, smoking, maternal age at consent, infant sex, and actual age at assessment. Values are mean and SD or number and percent, and treatment effects are differences in means or relative risks. Missing data have not been imputed. Continuous outcomes were analyzed by using linear regression. Adjusted models included as covariates center, parity, BMI category, SEIFA IRSD quintile, smoking, maternal age at consent, infant sex, and actual age at assessment. Outcomes presented as mean (SD) have effect estimates presented as mean difference, outcomes presented as n (%) have effect estimates as relative risk.

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