Does Soy Baby Formula Have Estrogen Is It Safe for Boy

Environ Health Perspect. 2011 Dec; 119(12): 1811–1816.

Research

Early-Life Soy Exposure and Gender-Role Play Beliefs in Children

Margaret A. Adgent

^oneDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina–Chapel Loma, Chapel Hill, Due north Carolina, USA

²Epidemiology Branch, National Institute for Environmental Health Sciences, National Institutes of Health, Department of Health and Man Services, Research Triangle Park, North Carolina, Us

Julie L. Daniels

^aneSection of Epidemiology, Gillings School of Global Public Health, University of North Carolina–Chapel Loma, Chapel Hill, North Carolina, USA

Lloyd J. Edwards

³Section of Biostatistics, Gillings School of Global Public Health, University of North Carolina–Chapel Hill, Chapel Hill, North Carolina, USA

Anna Maria Siega-Riz

¹Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina–Chapel Hill, Chapel Hill, North Carolina, Usa

Walter J. Rogan

²Epidemiology Branch, National Institute for Environmental Wellness Sciences, National Institutes of Wellness, Department of Wellness and Human being Services, Inquiry Triangle Park, North Carolina, Usa

Received 2011 Feb 15; Accepted 2011 Aug iii.

Abstract

Background: Soy-based infant formula contains loftier levels of isoflavones. These estrogen-similar compounds have been shown to induce changes in sexually dimorphic behaviors in animals exposed in early development.

Objective: We examined gender-role play behavior in relation to soy-based and not-soy-based infant feeding methods among children in the Avon Longitudinal Written report of Parents and Children.

Methods: Nosotros studied 3,664 boys and 3,412 girls. Four exposure categories were created using data from questionnaires administered at 6 and fifteen months postpartum: primarily breast, early on formula (referent), early on soy, and tardily soy. Gender-part play beliefs was assessed using the Pre-School Activities Inventory (PSAI). Associations between infant feeding and PSAI scores at 42 months of historic period were assessed using linear regression. Post hoc analyses of PSAI scores at 30 and 57 months were also conducted.

Results: Early-infancy soy utilise was reported for approximately ii% of participants. Mean [95% confidence interval (CI)] PSAI scores at 42 months were 62.three (62.0, 62.half dozen) and 36.9 (36.half-dozen, 37.2) for boys and girls, respectively. Subsequently adjustment, early soy (vs. early formula) feeding was associated with higher (less feminine) PSAI scores in girls (® = 2.66; 95% CI: 0.xix, 5.12) but was not significantly associated with PSAI scores in boys. The clan between soy exposure and PSAI scores in girls was substantially attenuated at 30 and 57 months.

Conclusions: Although not consistent throughout childhood, early-life soy exposure was associated with less female-typical play behavior in girls at 42 months of age. Soy exposure was non significantly associated with play behavior in boys.

Keywords: ALSPAC, endocrine disruptor, gender, infant formula, isoflavone, play behavior, PSAI, sexual dimorphism, soy

Soy-based baby formula (SBF) is a unremarkably used culling to cow milk–based infant formula, accounting for 12–20% of the babe formula sold in the United States and 2–7% in the United Kingdom (Bhatia et al. 2008; Committee on Toxicity of Chemicals in Food 2003; Essex 1996; National Toxicology Program 2010). Although SBF is considered to be nutritionally adequate for term infants (Bhatia et al. 2008), the overall safety of SBF has recently been debated because it contains high levels of the isoflavone compounds genistein and daidzein, plant-based compounds with structural and functional similarity to the steroid hormone 17®-estradiol ("phytoestrogens") (Badger et al. 2009; Barrett 2002; Chen and Rogan 2004; Setchell et al. 1997; Tuohy 2003; Vandenplas et al. 2010). These compounds can bind to estrogen receptors (ERs) with an affinity that is 100–ane,000 times less than that for estradiol and at to the lowest degree an guild of magnitude higher than that for the industrial endocrine-disrupting compound bisphenol A (Kuiper et al. 1998). Infants on an SBF diet have extremely high exposures to soy isoflavones, with urine isoflavone concentrations approximately 500 times those in cow milk formula–fed infants (Cao et al. 2009), merely the furnishings of isoflavone exposure in the postnatal period on child development are largely unknown. It is important to explore how early-life exposures to soy products may bear upon hormonally driven developmental outcomes.

Sexually dimorphic brain development and behavior are influenced by steroid hormones in the prenatal and early on postnatal periods (Arai et al. 1996; Davis et al. 1996; reviewed by Cohen-Bendahan et al. 2005; Dickerson and Gore 2007); thus, assessing the effects of early-life soy exposures on these end points is of nifty interest. Accordingly, animal models accept demonstrated that sexually dimorphic outcomes are sensitive to soy isoflavones. For case, the volume of sexually dimorphic regions of the brain (Faber and Hughes 1991, 1993; Lund et al. 2001a; Scallet et al. 2004), in addition to other dimorphic traits such every bit visual spatial retentivity (Lephart et al. 2002; Lund et al. 2001b) and mating behaviors (Kouki et al. 2003; Wisniewski et al. 2003), has been shown to be afflicted by phytoestrogen exposures in male person and female rats across a range of doses and life stages, albeit somewhat inconsistently (Lewis et al. 2003; Masutomi et al. 2003; Patisaul et al. 2007).

Human studies have similarly indicated that sexually dimorphic behaviors are susceptible to early-life hormone exposures, but little is known about the effects of postnatal estrogens. High prenatal androgen exposures have consistently been associated with girls' preference for male person-typical toys and interests in several studies of girls with congenital adrenal hyperplasia (Berenbaum and Hines 1992; Berenbaum et al. 2000; Iijima et al. 2001) and in studies of maternal and amniotic testosterone (Auyeung et al. 2009; Hines et al. 2002a). Contempo studies propose that postnatal testosterone may likewise be associated with male-typical evolution, as measured by sexually dimorphic auditory processing (Friederici et al. 2008) and social preferences in boys (Alexander et al. 2009).

The postnatal period is a fourth dimension of elevated hormonal activity (Andersson et al. 1998; Chellakooty et al. 2003), and the hypothalamus, which is integral in postnatal hormone regulation via the hypothalamic–pituitary–gonadal (HPG) centrality, has a concentration of ERs (Osterlund et al. 2000). It is plausible that ER bounden to isoflavones may interfere with normal HPG centrality function and, subsequently, disrupt regulated postnatal hormonal concentrations. Therefore, exploring the furnishings of postnatal soy exposures on sexually dimorphic evolution is warranted.

Observing gender-function play behaviors is a convenient method for assessing sexual dimorphism in young children. Characterized by a child'south preference for sure masculine- or feminine-typical toys, activities, and attitudes, gendered play behavior may be nowadays equally early as 12 months of age and typically becomes increasingly sexual activity specific with age (Golombok et al. 2008; O'Brien and Huston 1985; Servin et al. 1999; Snow et al. 1983). These characteristics, as measured by instruments such as the Pre-Schoolhouse Activities Inventory (PSAI), have been used to assess sexually dimorphic behaviors in children in previous studies of ecology endocrine disruptors, including phthalates, polychlorinated biphenyls, and dioxins (Swan et al. 2010; Vreugdenhil et al. 2002). Hither, we assessed the association between gender-role play behavior and infant feeding methods, with detail involvement in the effects of early-life soy exposure.

Materials and Methods

Study sample. Women who were pregnant, residing in the Avon region of the United Kingdom, and expected to deliver between i April 1991 and 31 Dec 1992 were eligible for the Avon Longitudinal Study of Parents and Children (ALSPAC); xiv,062 pregnancies were recruited into the study that resulted in alive births, and of these, 13,978 were twins or singletons alive at 1 year. The nowadays investigation was restricted to term singletons (n = 12,931) for whom consummate babe feeding data were available (n = 8,519) and for whom a play behavior consequence assessment was completed at approximately 42 months of age. The total report sample was 7,076 participants (3,664 boys and 3,412 girls). Mothers provided informed consent for participation. Ethical approval for the study was obtained from the ALSPAC Law and Ethics Committee and the Local Inquiry Ethics Committees. The nowadays analysis was approved by the Institutional Review Board of the University of North Carolina–Chapel Hill.

Exposure cess. Mothers completed babe feeding questionnaires at 1, six, 15, and 24 months postpartum. Mothers reported current breast-feeding habits, the age at which other milks or formulas were introduced into the kid'southward diet (including formula/baby milk, soy milk, soy formula, goat'southward milk, follow-on milk, hypoallergenic formula, and moo-cow's milk), and how many feedings per week were given for each of these products at the time of questionnaire completion.

We defined exposure categories using responses to the questionnaire administered at 6 months postpartum; if these data were missing or incomplete, responses from the 15-month questionnaire were used. "Early" exposure was defined as the use of a specific formula or milk type occurring ≤ 4 months of age ["At what age did you start (formula/milk blazon)?"] through ≥ vi months of historic period. Use at 6 months was indicated past any nonzero response to the question "How often nowadays is your baby fed (formula/milk type)?" in the six-month questionnaire. If the fifteen-month questionnaire was used instead, "early" exposure to formula was established for any participant that reported introducing the formula or milk ≤ four months of age and responded affirmatively to the question "Since your child was vi months sometime, has he/she had (formula/milk blazon)?" This definition established not but early on use of formula only besides a ane-month minimum duration of use.

We categorized participants into four mutually sectional feeding groups: primarily breast-fed, early on formula, early soy, and late soy (Figure 1). Primarily breast-fed infants were those who were breast-fed until ≥ six months of age who had no reported introduction of other milks or formulas before vi months of age and no reported soy milk/formula use before 24 months of age. Early formula-fed infants were those introduced to any nonsoy milk or formula product ≤ iv months of age, had sustained apply of such products at half-dozen months of historic period, and no reported soy use before 24 months of age. Early soy-fed infants were those introduced to soy milk or soy formula ≤ 4 months of historic period who had sustained employ at 6 months of age. Late soy-fed infants were those introduced to soy milk or soy formula any fourth dimension after four months of age through 15 months of historic period. We did not restrict the early formula, early soy, and late soy groups with respect to duration of breast-feeding; likewise, we did not restrict the early or late soy groups with respect to utilize of nonsoy formula.

Exposure label. Participants were classified into four mutually exclusive feeding groups (primarily breast, early formula, early soy, tardily soy). Participants who did not come across an exposure definition or who had incomplete feeding data were excluded. ^a Other: formula/baby milk, goat's milk, follow-on milk, hypoallergenic formula, and cow's milk. ^b Unknown: data bereft to make up one's mind breast-feeding duration or milk/formula use through 6 months. ^c Soy: soy milk or soy formula.

We excluded participants if feeding profiles were not sufficiently complete to estimate duration of a particular feeding method or if their known exposure profile did not fit into an exposure classification. We also excluded participants who reported soy apply but betwixt 15 and 24 months because we assumed that exposure would be low compared with earlier times in infancy. Responses from the 1-month questionnaire were used to verify that no soy was used in early on infancy amidst primarily breast-fed, early formula, and belatedly soy participants. Exposure definitions did not accept into account exposure to solid foods or their corresponding soy content, if whatever.

Outcome assessment. We used the PSAI, a psychometric test designed to assess inside and between gender differences in early-life play (Golombok and Rust 1993a, 1993b), to appraise gender-role play behavior. To complete the PSAI, mothers or other main caregivers reported how oftentimes their kid had played with sure toys (7 items), engaged in certain activities (11 items), and displayed sure characteristics (vi items) for the past month. Half of these items were "masculine," and half were "feminine." Each response was scored on a 5-point Likert scale, ranging from "never" to "very frequently." The instrument was scored past summing responses to masculine items, subtracting the sum of feminine items, and applying a transformation (48.25 + one.ane × score) to attain a "pseudo–t-score" (Golombok and Rust 1993b). Higher scores signal masculine typical beliefs, and lower scores signal feminine typical behavior.

PSAI assessments were administered in ALSPAC at 30, 42, and 57 months of age. We chose the 42-month assessment as our primary effect of interest, before whatsoever analysis, because this age was like to the age of the sample inside which the exam was validated (Golombok and Rust 1993b) and because this time betoken has been used in previous PSAI publications (Hines et al. 2002a, 2002b; Rust et al. 2000). In mail hoc analyses, nosotros used the 30- and 57-calendar month assessments to evaluate consistency of associations over time.

Covariates. Demographic, family composition, and lifestyle characteristics were assessed through parent report on self-completed questionnaires. The mother'south and partner's interaction with the child was estimated when the child was 42 months of age using a serial of questions assessing the frequency at which each parent participated in a list of eight activities with the child (score range, 0–36). Partner interaction scores were set to aught if the questionnaire reported that no partner was nowadays. We assumed partners were male, given a depression prevalence of mothers in same-sex partnerships in this cohort (< ane%) (Golombok et al. 2003).

Analysis. Crude mean PSAI scores were assessed as means with 95% confidence intervals (CIs) within exposure groups and within strata of each covariate. Adapted hateful differences in PSAI scores were estimated using multivariable linear regression. Boys and girls were modeled separately to distinguish inside-sex differences. The early formula-feeding group was used as the referent. We identified possible confounders as variables thought to be associated with gender part development and statistically associated with whatsoever babe feeding method in univariable investigations of these information (chi-square or t-test, p < 0.05, compared with early formula referent). Final models were adapted for age at assessment, presence of an older brother (yes/no) or an older sister (yes/no), regular child-care attendance (yes/no), maternal and partner interaction scores, and maternal factors, including age at delivery, smoking in the third trimester (yes/no), and education [ranked from high to depression: academy degree, advanced level, ordinary level, vocational, and Document of Secondary Teaching (CSE)/none].

Data were analyzed using both consummate case analysis and multiple imputation. For the complete case analysis, participants with missing data for aligning variables (~ eighteen%) were dropped from models, so only true values for participants with complete data were modeled. All analyses were completed using SAS (versions ix.one.3 and 9.ii; SAS Institute Inc., Cary, NC). For multiple imputation models, values for missing covariates were estimated from bachelor data on all adjustment variables, as well as breast-feeding duration and marital condition, using PROC MI (five iterations). Regression models of imputed data were run and summarized in PROC MIANALYZE.

Results

The characteristics of our study sample (due north = vii,076) and of all term singleton ALSPAC births (north = 12,931) are shown in Tabular array ane. When nosotros compared our study sample with participants excluded on the basis of insufficient data (n = 5,855; data not shown), included and excluded participants were similar with respect to sex, feeding method, and PSAI score distribution (among nonmissing). Still, the included sample had fewer children with older brothers (32.2% vs. 36.3%), older sisters (xxx.8% vs. 33.7%), and mothers who smoked (16.viii% vs. 24.0%) and more children with mothers property a university caste (15.1% vs. eleven.vii%), slightly older mothers (mean maternal age, 28.seven years vs. 27.ane years), and amend partner interaction (mean scores, twenty.3 vs. xix.7) than did participants that were excluded (proportions practice non business relationship for missing data). Amid the included participants, approximately 37% attended child-care regularly. About mothers were nonsmokers during the prenatal flow and had mid- to high-level education. Approximately six% of households reported the absence of a partner.

Table one

Characteristics of written report sample and eligible ALSPAC participants.

Study sample
Characteristic	Boys (n = 3,664)	Girls (n = 3,412)	Total (north = 7,076)	ALSPACa (northward = 12,931)
PSAI score (hateful ± SD)		62.3 ± 8.half dozen		36.ix ± ix.three		l.1 ± 15.5		fifty.0 ± 15.6
Missing (n)		—		—		—		3,580
Historic period at PSAI completion [months (mean ± SD)]		42.3 ± 0.viii		42.3 ± 0.8		42.3 ± 0.viii		42.three ± 0.ix
Missing (due north)		fourscore		83		163		3,809
Maternal age [years (hateful ± SD)]		28.ix ± 4.seven		28.6 ± 4.half dozen		28.7 ± iv.7		28.0 ± 5.0
Missing (northward)		0		0		0		0
Mother interaction score (mean ± SD)		28.5 ± 4.ix		28.8 ± iv.7		28.half dozen ± 4.8		28.6 ± 4.8
Missing (n)		8		3		11		three,597
Partner interaction score (hateful ± SD)		20.4 ± 7.9		xx.1 ± eight.1		xx.3 ± 8.0		20.1 ± 8.1
Missing (northward)		15		22		37		iii,638
Partner absent [n (%)]		216 (v.9)		219 (6.v)		435 (6.1)		609 (6.6)
Infant feeding method [n (%)]
Early formula		two,697 (73.half dozen)		2,488 (72.9)		5,185 (73.iii)		6,294 (73.9)
Early on soy		89 (ii.4)		68 (2.0)		157 (2.ii)		182 (2.1)
Late soy		167 (4.6)		139 (four.1)		306 (4.iii)		359 (4.two)
Primarily breast-fed		711 (19.4)		717 (21.0)		1,428 (xx.two)		ane,684 (19.8)
Missing (n)		—		—		—		4,412
Presence of older blood brother [n (%)]
No		2,344 (66.half-dozen)		2,261 (69.1)		four,605 (67.viii)		half dozen,816 (66.4)
Yes (≥ 1)		i,175 (33.4)		i,010 (30.9)		ii,185 (32.2)		3,443 (33.half-dozen)
Missing (n)		145		141		286		2,672
Presence of older sis [n (%)]
No		2,399 (68.2)		ii,294 (70.ii)		four,693 (69.two)		6,991 (68.2)
Yes (≥ 1)		1,118 (31.viii)		976 (29.8)		ii,094 (30.8)		3,264 (31.8)
Missing (due north)		147		142		289		two,676
Regular child care attendance [due north (%)]
No		2,229 (64.3)		2,017 (62.iii)		iv,246 (63.iii)		5,943 (63.0)
Yes		1,240 (35.7)		1,223 (37.7)		2,463 (36.7)		three,490 (37.0)
Missing (northward)		195		172		367		3,498
Prenatal smoking [northward (%)]
No		ii,924 (82.7)		2,769 (83.seven)		five,693 (83.2)		8,898 (80.5)
Yeah		611 (17.3)		539 (16.3)		1,150 (xvi.viii)		ii,162 (19.5)
Missing (n)		129		104		233		1,871
Maternal education [n (%)]
University caste		505 (14.7)		498 (15.half-dozen)		one,003 (fifteen.1)		1,497 (thirteen.8)
Advanced level		865 (25.ii)		826 (25.viii)		1,691 (25.5)		two,607 (24.1)
Ordinary level		i,316 (38.four)		one,195 (37.four)		two,511 (37.9)		4,002 (36.9)
Vocational		337 (ix.viii)		297 (ix.3)		634 (9.6)		1,132 (10.5)
CSE/none		406 (eleven.8)		379 (eleven.9)		785 (11.nine)		1,596 (14.seven)
Missing (n)		235		217		452		2,097
aEligible ALSPAC participants are limited to term, singleton infants live at 1 year.

Unless otherwise specified, all results pertain to the 42-month PSAI assessment. Boys' and girls' PSAI scores had distinct normal distributions [Figure 2; mean (95% CI), range: boys, 62.iii (62.0, 62.6), twenty.viii–95.six; girls, 36.9 (36.half dozen, 37.2), 4.3–85.vii] and were like to scores previously reported in this cohort (Golombok et al. 2008; Hines et al. 2002b). The PSAI assessment was completed between 41–53 months of age for boys and 41–54 months of age for girls. Early soy-fed infants accounted for ii.4% of boys and 2.0% of girls.

Distribution of 42-calendar month PSAI Scores past sex and feeding group for (A) girls and (B) boys.

Among girls, the hateful PSAI score [hateful (95% CI)] was highest (less feminine) with early soy feeding [40.8 (38.6, 43.0)] and lowest with early formula feeding [36.7 (36.4, 37.1)] (Table 2). Amid boys, PSAI scores were lowest (less masculine) in the primarily chest-fed group [61.3 (60.vi, 61.9)] and highest in the early soy-fed group [63.0 (61.3, 64.7)]. Withal, early soy feeding in boys was not associated with a hateful score that was significantly different from that of the early on formula-fed boys [62.six (62.2, 62.9)]. No pregnant difference was observed between late soy and early formula feeding for boys or girls or between breast-feeding and early formula feeding for girls.

Table 2

Crude mean PSAI scores and regression estimates (β) for exposure groups and select categorical and continuous covariates.

Covariate	Boys	Girls
Babe feeding method [mean PSAI score (95% CI)]
Early formulaa		62.6 (62.two, 62.9)		36.seven (36.4, 37.1)
Early soy		63.0 (61.three, 64.7)		40.8 (38.6, 43.0)
Late soy		62.1 (60.ix, 63.3)		37.0 (35.4, 38.six)
Primarily breast-fed		61.iii (60.six, 61.nine)		37.one (36.iv, 37.eight)
Presence of older blood brother [mean PSAI score (95% CI)]
Noa		61.six (61.2, 61.9)		35.nine (35.5, 36.3)
Yes (≥ one)		63.7 (63.ii, 64.2)		39.2 (38.seven, 39.8)
Missing		62.8 (61.4, 64.1)		36.2 (34.6, 37.7)
Presence of older sis [mean PSAI score (95% CI)]
Noa		63.2 (62.9, 63.6)		37.five (37.2, 37.9)
Yes (≥ i)		60.2 (59.vii, sixty.8)		35.v (34.9, 36.ane)
Missing		62.7 (61.three, 64.0)		36.two (34.7, 37.7)
Regular kid care attendance [mean PSAI score (95% CI)]
Noa		62.2 (61.ix, 62.vi)		36.7 (36.3, 37.1)
Yes		62.4 (61.ix, 62.9)		37.ii (36.seven, 37.8)
Missing		62.vii (61.4, 64.0)		37.1 (35.seven, 38.4)
Prenatal smoking [mean PSAI score (95% CI)]
Noa		62.0 (61.vii, 62.three)		36.7 (36.iii, 37.0)
Yes		63.vii (63.0, 64.4)		38.ii (37.4, 39.1)
Missing		62.0 (sixty.five, 63.6)		36.2 (34.5, 37.9)
Maternal instruction [mean PSAI score (95% CI)]
University degreea		60.5 (59.8, 61.iii)		38.6 (37.viii, 39.4)
Advanced level		62.0 (61.4, 62.half-dozen)		37.four (36.7, 38.0)
Ordinary level		62.seven (62.2, 63.one)		36.2 (35.vi, 36.7)
Vocational		62.4 (61.6, 63.3)		35.9 (34.ix, 36.9)
CSE/none		63.ii (62.iv, 64.1)		36.9 (36.0, 37.9)
Missing		63.2 (62.ane, 64.4)		36.half-dozen (35.iii, 37.8)
Age at PSAI assessment [β (95% CI)]		0.24 (–0.12, 0.60)		–0.46 (–0.85, –0.08)
Maternal age at commitment [β (95% CI)]		–0.02 (–0.08, 0.04)		0.17 (0.11, 0.24)
Maternal interaction score [β (95% CI)]		0.02 (–0.04, 0.08)		0.01 (–0.05, 0.08)
Partner interaction score [β (95% CI )]		0.00 (–0.03, 0.04)		0.02 (–0.02, 0.06)
aReferent category.

In the adjusted complete case analysis, early soy feeding was as well significantly associated with higher PSAI scores among girls [® = 2.66 (95% CI: 0.xix, 5.12)], whereas primarily breast-feeding was associated with significantly lower scores in boys [® = –0.80 (95% CI: –1.57, –0.03)], compared with early formula feeding (Table 3). Scores were higher among the early soy-fed boys compared with early formula feeding, merely this difference was non significant. Associations for early soy exposure derived using multiple imputation were like but more precise [® (95% CI): girls, 2.83 (0.63, 5.02); boys, 0.90 (–0.88, ii.68)]. No notable clan was observed in the late soy exposure grouping for either sex.

Table 3

Adjusteda difference in mean PSAI scores for boys and girls from complete instance analysis.

β-Coefficient (95% CI)
Covariate	Boys (n = three,010)	Girls (north = ii,823)
Infant feeding method
Early on formula		0		0
Early soy		1.18 (–0.73, 3.09)		2.66 (0.19, 5.12)
Tardily soy		–0.53 (–1.98, 0.91)		–0.03 (–1.78, 1.71)
Primarily chest-fed		–0.80 (–1.57, –0.03)		–0.26 (–1.10, 0.58)
Presence of older blood brother
No		0		0
Yes (≥ i)		2.06 (ane.39, 2.73)		three.24 (2.48, 4.00)
Presence of older sister
No		0		0
Yes (≥ 1)		–ii.75 (–3.42, –ii.08)		–1.89 (–2.65, –ane.xiii)
Regular child care attendance
No		0		0
Yes		0.32 (–0.31, 0.96)		0.41 (–0.29, i.10)
Prenatal smoking
No		0		0
Yes		1.42 (0.57, 2.27)		2.08 (1.11, 3.05)
Maternal education
University caste		0		0
Advanced level		1.29 (0.31, 2.27)		–ane.31 (–2.37, –0.24)
Ordinary level		2.01 (i.05, 2.97)		–2.59 (–iii.65, –ane.53)
Vocational		1.71 (0.41, 3.00)		–2.74 (–4.17, –1.30)
CSE/none		two.48 (1.22, iii.74)		–2.21 (–3.61, –0.81)
Age at PSAI assessment		0.13 (–0.27, 0.53)		–0.64 (–i.10, –0.xviii)
Maternal age		0.06 (–0.01, 0.thirteen)		0.10 (0.01, 0.18)
Maternal interaction score		0.03 (–0.03, 0.ten)		0.02 (–0.06, 0.09)
Partner interaction score		0.01 (–0.03, 0.05)		0.03 (–0.02, 0.07)
aAdjusted model includes all variables shown hither.

For both sexes, the adjusted hateful departure in PSAI score was college if an older brother was present in the home or if the mother smoked prenatally and lower if an older sister was nowadays. With increasing maternal pedagogy, scores more often than not decreased for boys and increased for girls, suggesting that highly educated mothers were more likely to report a mixture of masculine and feminine traits, regardless of their child's sexual practice, than were less educated mothers. Age at assessment and maternal age were associated with lower and higher scores among girls, respectively. These findings are by and large similar to previous reports on this cohort (Hines et al. 2002b; Rust et al. 2000).

In post hoc analyses, mean PSAI scores [mean (95% CI)] at 30 and 57 months were higher in early soy-fed girls [42.7 (40.3, 45.1) and 36.9 (34.4, 39.v), respectively] compared with the early formula referent [xl.5 (40.2, xl.ix) and 35.2 (34.8, 35.6), respectively]. All the same, the mean difference between these exposure groups weakened at both time points after adjustment for age at assessment, maternal education, maternal age, presence of older brother, presence of older sis, and prenatal smoking [® (95% CI): 30 months, 0.55 (–i.58, 2.69); 57 months, 0.64 (–ane.87, iii.15)]. Associations between PSAI scores at 30 and 57 months and primarily breast-feeding among boys were consequent with the association at 42 months [® (95% CI): thirty months, –0.89 (–1.sixty, –0.19); 57 months, –1.09 (–1.91, –0.26)].

Discussion

Early on-life soy exposure was associated with a slightly higher PSAI score among girls at 42 months of age, whereas soy exposure and PSAI scores were positively but not significantly associated in boys. The increase in PSAI scores amidst early soy-exposed girls was small and did not place them exterior the range of normal female behavior, but it was robust to aligning for strong predictors of behavior, including the presence of an older brother or sis. In fact, the event size observed in soy-exposed girls was similar to that observed in girls with older brothers, although much less precise.

Amongst early soy-fed girls, associations with the 30- and 57-month assessments were weaker than our chief findings for the 42-month assessment, suggesting that our main findings may be overestimated. All the same, because boys' and girls' behaviors get increasingly sexual activity specific with age (Golombok et al. 2008), it is likewise possible that the influence of an ecology factor such every bit soy may get more or less important over time. These boosted analyses encourage cautious interpretation of our findings but do non invalidate them.

Nosotros also observed that boys who were primarily breast-fed had lower PSAI scores at all fourth dimension points than did boys fed nonsoy formula. Duration of breast-feeding has previously been associated with feminized play behavior in girls only not in boys (Sandberg et al. 2003). In both sexes, an inconsistent association between breast-feeding and externalizing behavior has likewise been reported (Kramer et al. 2008; Samarakkody et al. 2011). However, studies of breast-feeding and child development are often met with issues of unmeasured misreckoning related to differences between breast-feeding and formula-feeding mothers that are typically greater than differences betwixt users of unlike types of formula. Accordingly, the relationship observed in our written report may exist confounded by unmeasured factors associated with a mother'southward choice to breast-feed and her attitudes toward gender roles in male person children. Therefore, despite a consistent association over time, this finding warrants further study before meaningful conclusions can be fatigued.

Our findings among early on soy-exposed girls are supported by a modest literature. In female rats, the volume of the sexually dimorphic nucleus of the medial preoptic area of the hypothalamus has been shown to increase (Faber and Hughes 1991, 1993), and reproductive posturing behaviors accept been altered after neonatal exposure to high levels of genistein (Kouki et al. 2003). Other estrogenic compounds, such equally diethylstilbestrol, accept also been shown to induce express masculinization of beliefs in female primates, but not humans, after prenatal exposure (Goy and Deputte 1996; Lish et al. 1991). In addition, sex differences in response to soy exposure have been suggested in a recent written report demonstrating that preschool-age girls excrete increasing levels of urinary testosterone, whereas boys excrete decreasing levels of urinary estrogens, with increasing dietary soy consumption (Wada et al. 2011).

The susceptibility of neurodevelopmental processes to postnatal endocrine disruption is unclear. Visual preference for groups (i.e., multiple individuals) over solitary individuals, a male person-typical trait, has been associated with postnatal testosterone concentrations in male person infants, suggesting that some gender-typical preferences may be susceptible to postnatal endocrine disruption (Alexander et al. 2009). All the same, to our cognition, no studies to date take reported an association betwixt postnatal endocrine activity and visual, social, or other gender-typical preferences in girls, and potential mechanistic explanations are sparse.

In this study, soy production use in early on and belatedly infancy was characterized using longitudinal exposure assessment. Nevertheless, soy users were not necessarily exclusively fed soy products at any fourth dimension, and we could not narrate the relative dose of soy. Thus, we could not appraise a dose–response relationship between soy feeding and PSAI score or account for other dietary exposures to soy isoflavones. Improved characterization of early-life soy exposure, either through more than detailed questionnaires or isoflavone biomarkers, should be practical in future studies.

Conclusions

Our study suggests that early-life exposure to soy products may subtly reduce female-typical play behaviors in girls at 42 months of age. Given the low prevalence of soy use in this study sample, associations between soy exposure and PSAI score were imprecise, and results should exist interpreted cautiously. An association between chest-feeding and play behavior in boys was also observed just may exist heavily confounded by unmeasured lifestyle factors, given the broad differences that generally persist between breast-feeding and formula-feeding mothers. The associations observed here were modest, and the mean PSAI score for all exposure groups was still within the range of normal behavior for each sexual practice. Replication of these findings in other populations is needed, particularly in ones with more than prevalent SBF utilize.

Acknowledgments

Nosotros are grateful to all the families who took part in this written report, the midwives for their aid in recruiting them, and the Avon Longitudinal Report of Parents and Children (ALSPAC) team, including interviewers, calculator and laboratory technicians, clerical workers, enquiry scientists, volunteers, managers, receptionists, and nurses. The U.K. Medical Research Council (grant 74882), the Wellcome Trust (grant 076467), and the University of Bristol provide cadre support for ALSPAC.

Footnotes

This enquiry was specifically funded by Eunice Kennedy Shriver National Constitute of Child Health and Human Development, National Institutes of Health (NIH; T32HD052468-01A2), 2008–2013, and the Intramural Research Program of the NIH.

The authors declare they take no actual or potential competing financial interests.

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261982/

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