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Mother’s voice and heartbeat sounds elicit auditory
plasticity in the human brain before full gestation
Alexandra R. Webb
a
, Howard T. Heller
b
, Carol B. Benson
b
, and Amir Lahav
a,c,1
a
Department of Pediatrics Newborn Medicine and
b
Department of Radiology, Brigham and Women’s Hospital, Boston, MA 02115; and
c
Department of
Pediatrics, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02115
Edited by Mortimer Mishkin, National Institute for Mental Health, Bethesda, MD, and approved January 28, 2015 (received for review August 6, 2014)
Brain development is largely shaped by early sensory experience.
However, it is currently unknown whether, how early, and to
what extent the newborn’s brain is shaped by exposure to mater-
nal sounds when the brain is most sensitive to early life program-
ming. The present study examined this question in 40 infants born
extremely prematurely (between 25- and 32-wk gestation) in the
first month of life. Newborns were randomized to receive auditory
enrichment in the form of audio recordings of maternal sounds
(including their mother’s voice and heartbeat) or routine exposure
to hospital environmental noise. The groups were otherwise medi-
cally and demographically comparable. Cranial ultrasonography
measurements were obtained at 30 ±3 d of life. Results show that
newborns exposed to maternal sounds had a significantly larger
auditory cortex (AC) bilaterally compared with control newborns re-
ceiving standard care. The magnitude of the right and left AC thick-
ness was significantly correlated with gestational age but not with
the duration of sound exposure. Measurements of head circumfer-
ence and the widths of the frontal horn (FH) and the corpus callosum
(CC) were not significantly different between the two groups. This
study provides evidence for experience-dependent plasticity in the
primary AC before the brain has reached full-term maturation. Our
results demonstrate that despite the immaturity of the auditory path-
ways, the AC is more adaptive to maternal sounds than environmen-
tal noise. Further studies are needed to better understand the neural
processes underlying this early brain plasticity and its functional impli-
cations for future hearing and language development.
auditory
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brain
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mother’s voice
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heartbeat
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preterm newborns
One of the first acoustic stimuli we are exposed to before
birth is the voice of the mother and the sounds of her
heartbeat. As fetuses, we have substantial capacity for auditory
learning and memory already in utero (1–5), and we are partic-
ularly tuned to acoustic cues from our mother (6–9). Previous
research suggests that the innate preference for mother’s voice
shapes the developmental trajectory of the brain (10, 11). Pre-
natal exposure to mother’s voice may therefore provide the brain
with the auditory fitness necessary to process and store speech
information immediately after birth (12, 13).
There is evidence to suggest that prenatal exposure to the ma-
ternal voice and heartbeat sounds can pave the neural pathways in
the brain for subsequent development of hearing and language
skills (14). For example, the periodic perception of the low-fre-
quency maternal heartbeat in the womb provides the fetus with an
important rhythmic experience (15, 16) that likely establishes the
neural basis for auditory entrainment and synchrony skills necessary
for vocal, gestural, and gaze communication during mother–infant
interactions (17, 18).
Studies examining the neural response to the maternal voice
soon after birth have found activation in posterior temporal
regions, preferentially on the left side, as well as brain areas
involved in emotional processing including the amygdala and
orbito-frontal cortex (19). Similarly, Beauchemin et al. have
found activation in language-related cortical regions when new-
borns listened to their mother’s voice, whereas a stranger’s voice
seemed to activate more generic regions of the brain (20). In
addition, Partanen et al. have shown that the neural response to
maternal sounds depends on experience as full-term newborns
react differentially to familiar vs. unfamiliar sounds they were
exposed to as fetuses, suggesting correlation between the amount
of prenatal exposure and brain activity (21). Taken together, the
above studies suggest that the mother’s voice plays a special role
in the early shaping of auditory and language areas of the brain.
Numerous animal studies have shown that brain development
relies on developmentally appropriate acoustic stimulation early
in life (22–32). Auditory deprivation during critical periods can
adversely affect brain maturation and lead to long-lasting neural
despecialization in the auditory cortex (AC), whereas auditory
enrichment in the early postnatal period can enhance neural
sensitivity in the primary AC, as well as improve auditory recog-
nition and discrimination abilities.
Preterm infants are born during a critical period for auditory
brain development. However, the maternal auditory nursery pro-
vided by the womb vanishes after a premature birth as the preterm
newborn enters the neonatal intensive care unit (NICU). The
abrupt transition of the fetus from the protected environment of the
womb to the exposed environment of the hospital imposes signifi-
cant challenges on the developing brain (33). These challenges have
been associated with neuropathologic consequences, including re-
duction in regional brain volumes, white matter microstructural
abnormalities, and poor cognitive and language outcomes in pre-
term compared with full-term newborns (34–41).
Considering the acoustic gap between the NICU environment
and the womb, it is not surprising that auditory brain development
is compromised in preterm compared with full-term infants (42,
43). Numerous studies have suggested that the auditory environ-
ment available for preterm infants in the NICU may not be con-
ducive for their neurodevelopment (44–47). These concerns are
Significance
Newborns can hear their mother’s voice and heartbeat sounds
before birth. However, it is unknown whether, how early, and to
what extent the newborn’s brain is shaped by exposure to such
maternal sounds. This study provides evidence for experience-
dependent plasticity in the auditory cortex in preterm newborns
exposed to authentic recordings of maternal sounds before full-
term brain maturation. We demonstrate that the auditory cortex is
more adaptive to womb-like maternal sounds than to environ-
mental noise. Results are supported by the biological fact that
maternal sounds would otherwise be present in utero had the baby
not been born prematurely. We theorize that exposure to maternal
sounds may provide newborns with the auditory fitness necessary
to shape the brain for hearing and language development.
Author contributions: A.R.W., H.T.H., C.B.B., and A.L. designed research; A.R.W., H.T.H.,
and A.L. performed research; A.R.W., H.T.H., C.B.B., and A.L. contributed new reagents/
analytic tools; A.R.W., H.T.H., and A.L. analyzed data; and A.R.W., H.T.H., C.B.B., and A.L.
wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
1
To whom correspondence should be addressed. Email: amir@hms.harvard.edu.
www.pnas.org/cgi/doi/10.1073/pnas.1414924112 PNAS Early Edition
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derived from the frequent reality that hospitalized preterm new-
borns are overexposed to loud, toxic, and unpredictable environ-
mental noise generated by ventilators, infusion pumps, fans,
telephones, pagers, monitors, and alarms (48–51), whereas at the
same time they are also deprived of the low-frequency, patterned,
and biologically familiar sounds of their mother’svoiceand
heartbeat, which they would otherwise be hearing in utero (33, 45).
In addition, the hospital environment contains a significant amount
of high-frequency electronic sounds (52, 53) that are less likely to
be heard in the womb because of the sound attenuation provided
by maternal tissues and fluid within the intrauterine cavity (54–56).
Efforts to improve the hospital environment for preterm neonates
have primarily focused on reducing hospital noise and maintaining
a quiet environment. However, exposing medically fragile preterm
newborns to low-frequency audio recordings of their mothers on
a daily basis has been less acknowledged to be of necessity, and the
extent to which such maternal sound exposure can influence brain
maturation after an extremely premature birth has been a matter
of much debate.
The present study aimed to determine whether enriching
the auditory environment for preterm newborns with authentic
recordings of their mother’s voice and heartbeat sounds in the
first month of life would result in structural alterations in the
AC. The rationale driving this question lies in the fact that
such enriched maternal sound stimulation would otherwise be
present had the baby not been born prematurely.
Results
As shown in Table 1, the maternal sounds and control groups did
not significantly differ in the following characteristics: sex, birth
gestational age, birth weight, 1-min Apgar, 5-min Apgar, head
circumference and postmenstrual age at 1-mo cranial ultrasound,
days on mechanical ventilation, and administration of antenatal
corticosteroids.
Results were based on structural measurements of the AC, the
frontal horn (FH), and the corpus callosum (CC) obtained by
cranial ultrasonography (Fig. 1). AC thickness was significantly
different between the groups [F(2, 37) =10.10, P<0.001] (Fig. 2).
Infants in the maternal sounds group had a significantly larger right
and left AC compared with infants in the control group [F(1, 38) =
20.45, P<0.001 and F(1, 38) =6.55, P=0.015, respectively]. The
width of the FH and the CC were not significantly different
between the two groups [F(2, 37) =0.90, P=0.413 and t(38) =
0.56, P=0.578, respectively] (Fig. 2 and Table 2).
Spearman correlational analysis revealed that, in both groups,
the magnitude of the right and left AC thickness was signifi-
cantly correlated with gestational age (for right AC and gesta-
tional age: maternal sounds: ρ=−0.55, P=0.01; controls:
ρ=−0.60, P=0.007; and for left AC and gestational age: maternal
sounds: ρ=−0.56, P=0.008; controls: ρ=−0.51, P=0.02). The
measurements of the control brain regions (FH and CC) were not
significantly correlated with gestational in either group.
Finally, within the maternal sound group, the average duration
of sound exposure was 23.6 d with a narrow distribution (SD =
3.4), which was insufficient to significantly correlate with any of
the AC measures (right AC: ρ=−0.12, P=0.59; left AC: ρ=
+0.09, P=0.68).
Discussion
This study examined the effect of sound exposure on brain de-
velopment in hospitalized preterm newborns. We compared the
exposure effects between unfiltered hospital noise (currently the
standard of care) vs. a modified care practice, which includes daily
auditory enrichment in the form of low-pass filtered recordings of
mother’s voice and heartbeat sounds. Our results demonstrate au-
ditory brain plasticity induced by exposure to womb-like maternal
sounds in preterm newborns. Newborns receiving added exposure
to mother’s voice and heartbeat sounds in the early postnatal period
showed significantly larger AC at 1 mo of age compared with
control newborns receiving routine care. The magnitude of the
right and left AC thickness was significantly correlated with ges-
tational age at birth. The negative direction of the correlations
indicates that younger babies had larger AC measurements relative
to the transtemporal diameter (TTD) of their brain, suggesting
that the relative size of AC is more pronounced earlier in gesta-
tion. As we discuss below, this study illustrates a highly specific
modifiability within the AC in response to maternal sounds and
highlights the importance of the newborn’s sensory experience
during postnatal hospitalization.
Our findings of auditory brain plasticity before full gestation
are in keeping with several studies, primarily by Merzenich and
colleagues, showing that early auditory experience, either in the
form of enrichment or impoverishment, can have a substantial
impact on both the structural and functional development of the
AC in rat pups (26, 27, 29, 31, 57, 58). Similarly, an established
body of work by Lickliter and colleagues has shown that
Table 1. Newborn characteristics
Parameters Maternal sounds Control Pvalue
Subjects, n21 19 NA
Female, n(%) 9 (43) 4 (21) 0.141
Birth GA (wk) 28.9 ±1.9 29.6 ±2.1 0.262
Birth weight (g) 1,310 ±344 1,397 ±369 0.441
1-min Apgar 5.48 ±2.50 5.26 ±1.91 0.766
5-min Apgar 7.29 ±1.52 7.68 ±1.00 0.537
HC at 1-mo cUS (cm) 29.3 ±2.6 29.9 ±2.8 0.481
PMA at 1-mo cUS (wk) 33.06 ±1.92 33.87 ±2.12 0.211
Mechanical ventilation (d) 2.52 ±2.87 3.47 ±8.08 0.616
Antenatal corticosteroids, n(%) 13 (62) 11 (58) 0.796
cUS, cranial ultrasound; GA, gestational age; HC, head circumference;
NA, not applicable; PMA, postmenstrual age.
Fig. 1. Shown are measurements (white lines) of the (A) thickness of the AC in the coronal plane, (B) width of the FH of the lateral ventricle in the coronal
plane, and (C) width of the body of the CC in the midsagittal plane.
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bobwhite quail chicks receiving auditory stimulation early in
embryogenesis demonstrated improved auditory learning and
memory when tested postnatally (59–61). The collective im-
pression of the above studies indicates that the early postnatal
period provides a critical window of opportunity wherein sensory
enrichment or sensory deprivation can play a major role in the
development of the auditory brain system.
It is important to highlight that newborns in the maternal
sound group were exposed to premixed audio recordings that
included both the maternal voice and the maternal heartbeat
played at the same time, much like they would have otherwise
experienced had they not been born prematurely and were still in
the womb. The concurrent inclusion of both the maternal
heartbeat and the maternal voice on a single audio track was
necessary to simulate the in utero experience, consistent with
previous protocols used in recent studies from our laboratory
(62, 63). Therefore, the present study cannot determine the
relative contribution of mother’s voice vs. the maternal heartbeat
to the observed effects on auditory brain development.
To add an additional layer of biological authenticity to our
maternal sound stimulation, newborns in the maternal sound
group were intentionally exposed to a low-pass filtered version of
the maternal sounds recordings, which naturally eliminated most
segmental speech information. Low-pass filtering usually dis-
rupts the intelligibility of individual syllables and speech rate in
the utterances, and the resulting muffledness makes prosody the
primary acoustic element contributing to auditory perception
(64, 65). It is therefore tempting to speculate that the sole pro-
sodic information of the maternal sounds stimulus was sufficient
to yield the observed increase in cortical thickness of the AC
among our preterm newborn listeners. Prosodic features, such as
melody, intensity, and rhythm, are known to be essential for
language acquisition, and there is compelling evidence to suggest
that newborns are strongly influenced by prosodic features of
their native language long before first words are even produced
(66–69). The question of whether daily exposure to unfiltered
maternal sounds would result in different structural patterns
of brain maturation is still unclear and needs to be investigated
in future studies.
Our results suggest that daily exposure to biologically mean-
ingful acoustic stimulation in the form of mother’s voice and
heartbeat sounds, even for a relatively short duration of time (i.e.,
3 h/d), was yet sufficient to yield structural changes in the de-
veloping auditory cortex. One should bear in mind that for the vast
majority of the time, newborns in the maternal sounds group were
exposed to routine noises in the hospital environment, much like
infants in the control group. The exposure difference between the
groups comes down to only 3 h of recorded maternal sound ex-
posure per day. It is therefore striking that newborns exposed to
recorded maternal sounds demonstrated significant microstruc-
tural plasticity in the AC with minimal dosage and within less than
1 mo of exposure. These rapid changes are particularly interesting
given that the rate of microstructural brain maturation in preterm
newborns has been previously correlated with cortical growth, and
predicted higher developmental test scores at 2 y of age (70).
Although the auditory brain system undergoes experience-
dependent plasticity across the lifespan (71), it is theorized that
the probability of such plasticity may be higher and much needed
during critical periods when the underlying developmental pro-
cesses are still in flux, such as following a premature birth. In
future studies, it would be interesting to test whether added ex-
posure to maternal sounds in the early postnatal period can better
facilitate synaptic pruning and neural migration in the AC than
exposure to hospital environmental noise, a question that was
beyond the scope of the present study and is yet to be determined.
Notably, exposure to maternal sounds in our study did not
seem to influence overall brain growth, but instead led to a
rather region-specific structural plasticity in the AC, a brain area
that is most intuitively expected to be affected by the auditory
stimulation. The fact that both newborns’head circumference
(Table 1) and the width of the lateral ventricular horns (Table 2)—
measures that have been previously correlated with total brain
tissue volume (72)—did not significantly differ between the groups
may be taken as evidence that the neuroplasticity induced by
maternal sounds did not appear to increase overall brain matter,
consistent with the specialized nature of experience-dependent
plasticity (73, 74).
The possibility that newborns in the control group had smaller
AC to begin with has been ruled out by our method of analysis,
by which we normalized the size of the AC for each infant based
on the TTD of the brain. This normalized measure represents
the cortical thickness of the AC compared with the size of the
brain, accounting for any possible differences between the
groups in AC size before the study onset. Future ultrasonogra-
phy studies, using a volume probe and a repeated-measure de-
sign over a longer period are needed to determine the effects of
exposure to maternal sounds on total brain volume at term-
equivalent age and beyond.
The bilateral plasticity in the AC is noteworthy. Given the
linguistic nature of the stimulus the newborns were exposed to
(i.e., maternal speech sounds), one might expect the effect to be
primarily on the left side of the brain because of the functional
lateralization typically seen in the adult brain when processing
speech (75–78). However, it is possible that because the preterm
newborns in our study were at a very early stage of development,
essentially at an age equivalent to the last trimester of pregnancy
and before full gestation, their brains had not yet begun to ex-
hibit hemispheric specialization for speech, and thereby auditory
neuroplasticity occurred more globally on both sides of the AC.
0
1
2
3
4
5
6
R-AC L-AC R-FH L-FH CC
Size normalized by TTD
Brain structures
Maternal Sound
Control
*
*
Fig. 2. Mean brain measurements are shown for the maternal sounds (blue)
and control (red) groups in normalized arbitrary units, including the right
and left AC thickness (R-AC and L-AC), right and left FH width (R-FH and
L-FH), and width of the body of the CC. All measurements were individually
normalized by the transtemporal diameter (TTD) of the newborn. Error bars
represent SD. Asterisks denote statistically significant results (P<0.05); values
are given in Table 2.
Table 2. Anatomical size of brain structures
Brain structure (width) Maternal sounds Control Pvalue
Auditory cortex
R-AC 4.16 ±0.94 3.11 ±0.44 0.000
L-AC 3.62 ±0.95 2.96 ±0.68 0.015
Frontal horn
R-FH 1.50 ±1.07 2.00 ±1.66 0.270
L-FH 2.15 ±1.20 2.31 ±1.75 0.723
Corpus callosum 4.72 ±0.64 4.59 ±0.73 0.578
Measurements normalized for each infant by the TTD.
Webb et al. PNAS Early Edition
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An alternative hypothesis to explain the bilateral plasticity in the
AC in the present study can be supported by a growing body of
research, suggesting that the apparent left-sided lateralization
for speech and language processing, specifically in the AC, is not
an absolute dominance but rather a shared expertise by the two
hemispheres (79–81). The above hypotheses must be made with
caution because at this premature age, cortical folding is still in
flux and the majority of neurons are still migrating and have not
yet reached their final cortical destination. Thus, brain imaging
at this age can only provide a snapshot in time of the current
developmental course and no firm conclusions regarding per-
manent hemispheric dominancy can be drawn based on the
present study. In addition, the early onset of left hemispheric
differentiation in newborns is primarily based on functional
rather than structural evidence. Previous studies in preterm
neonates have found left-hemispheric functional advantage for
speech processing in the posterior temporal region, as indicated
by faster and more sustained responses to speech sounds over the
left than over the right hemisphere (82). These findings are
consistent with similar results suggesting that infants are born with
a left hemisphere functional specialization for speech processing
(83–85). The ultrasound data obtained in our study are solely based
on structural measurements, and thus our findings cannot dispute or
support the above-mentioned studies. However, our results indicate
that newborns in the maternal sounds group had larger AC on the
right compared with the left side of the brain (Fig. 2). Although this
difference was not statistically significant, it is congruent with pre-
vious evidence showing that many sulci appear 1–2 wk earlier on the
right than on the left side of the brain, with larger temporal sulci on
the right hemisphere (86, 87).
Interestingly, we found no differences in CC size between the two
groups of newborns in our study. The CC was chosen as a control
region because of its central location and global role in inter-
hemispheric communication, connecting the auditory areas be-
tween the two hemispheres (88). In addition, because the size of the
CC is known to correlate with overall brain volume, we assumed
that the CC may have a good predictive value for experience-
dependent changes of global brain growth (89). Previous studies
have found increased CC size in musicians (90, 91), although it is
unclear whether this effect was solely caused by enhanced auditory
stimulation or a more integrated influence of the multisensory ex-
perience (visual, auditory, motor, and tactile) associated with intense
musical training (92). The fact that exposure to maternal sounds in
our study did not elicit significant structural changes in the CC does
not rule out the possibility that these changes would eventually
occur at a later gestational age or with longer exposure periods.
Further studies are needed to determine the degree of neural
specificity and experience-dependent plasticity induced by maternal
sounds exposure in preterm infants undergoing intensive care.
In considering the clinical relevance of our results, the limi-
tations of cranial ultrasonography should be discussed. Although
cranial ultrasound is the diagnostic imaging of choice for ruling
out the appearance of brain pathology in the population of
high-risk preterm neonates (93–96), and clearly an acoustically
quieter examination than an MRI, some consider MRI to be
more accurate. Linear measurements from cranial ultrasound
have been strongly correlated with major neonatal cerebral sites
seen on MRI (72, 93, 97–99), although several regions, including
the posterior horn depth of the lateral ventricle and the cortex of
the cingulate gyrus, may appear to be slightly narrower than when
measured sonographically (97). For that reason, in the present
study we intentionally chose not to focus on absolute values of
brain measurements, but rather report normalized values based on
the TTD of each infant. In the absence of MRI data available for
our cohort of newborns, this approach allowed us to reliably ex-
amine the difference in brain structures between the groups re-
gardless of whether or not the measurements correlate with MRI.
To summarize, this study provides evidence for auditory cortex
plasticity in preterm newborns receiving daily exposure to ma-
ternal sounds in the first month of life. The functional implica-
tion of this early brain plasticity is still unclear and warrants
further investigation. We theorize that exposing preterm new-
borns to mother’s voice and heartbeat sounds provides them with
a biologically familiar sensory experience that may play an
important role in negating the effects of the noxious hospital
environment on brain development. In addition, the use of
recorded maternal sounds in the first month of life may be es-
pecially helpful in this high-acuity population of newborns whose
exposure to live maternal stimulation is often limited because of
infrequent parental visits. Despite the prospects of these results,
the clinical benefits of maternal sound exposure are still a matter
of speculations and no firm conclusions can be drawn based on
the present study. Clearly, preterm newborns have more working
against them than can be fully compensated for by added ex-
posure to maternal sounds. However, the present study begins
to show the effect that maternal sounds could have on very early
brain development. Further studies are needed to determine the
functional implications of these results and their predictive value
of long-term hearing and language outcomes.
Materials and Methods
Patient Population. Forty preterm newborns admitted to the NICU at Brigham
and Women’s Hospital participated in this study. Newborns were randomized
to one of two groups. A description of the study population is given in Table 1.
Inclusion criteria included gestational age at birth between 25 and 32 wk and
available records of cranial ultrasounds at one month of age. Exclusion criteria
included prenatal diagnosed brain lesions, intracranial hemorrhage, cystic
periventricular leukomalacia, prominent extra-axial spaces, and dilated lateral
ventricular atria. Additional restrictive exclusion criteria were included to en-
sure our results would not be skewed by common conditions known to alter
brain anatomy, such as small for gestational age (100) and intrauterine growth
restriction (101, 102). A written informed consent was obtained from parents.
Maternal Sound Group. Newborns in the maternal sounds group (n=21) re-
ceived daily exposure to audio recordings of their mother’s voice and heartbeat
sounds played inside their incubator for a total of 3 h/d (four times per day for
a duration of 45 min each). Maternal sounds were not played between midnight
and 5:00 AM and were avoided during parental visits or medical examinations.
Environmental Sound Group (Control). Control preterm newborns (n=19)
were exposed to unfiltered routine hospital noise as present in the NICU
environment with no added exposure to audio recordings of their mother’s
voice and heartbeat sounds. The acoustic properties of the NICU environ-
ment were measured in a separate study. Noise measurements taken in our
NICU revealed an average higher noise levels during daytime (Leq =60.05
dBA) compared with night-time (Leq =58.67 dBA). Spectral analysis of fre-
quency bands (>50 dB) showed that infants were exposed to frequencies to
high-fervency sounds >500 Hz 57% of the time (53).
Maternal Sound Exposure. Mother’s voice was recorded individually for each
infant. Voice recording was done in a standardized fashion via a large-
diaphragm condenser microphone (KSM44, Shure), capturing three types of
vocalizations (speaking, reading, and singing) from each mother. Voice re-
cordings were attenuated using a low-passfilterwithacut-offof400Hzto
mimic the low frequency womb-like experience. The mater nal v oice re-
cording was overlaid with individualized recordings of the mother’s
heartbeat using a digital stethoscope (ds32a; Thinklabs Digital Stethoscopes).
This was done in an attempt to simulate the auditory experience in utero
wherein the fetus hears both the mother’s voice and the sounds of her
heartbeat simultaneously. The maternal recordings were loaded onto an MP3
player (Phillips Electronics, SA2RGA04KS) for playback inside the incubator via
a micro audio system. Loud peaks >65 dBA (A-weighted) of the maternal sound
recordings were attenuated to achieve a safe level of sound delivery as was
measured by a sound level meter (Bruel & Kjaer, 2250), approximating the level
of normal human conversation (Mean LAq =58.6 dBA). The above protocol was
administered individually for each infant randomized to the maternal sounds
group as validated in a previous safety and feasibility study (103), as well as in
several experimental reports from our group (63, 104, 105).
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Neonatal Cranial Ultrasound Measurements. All neonatal cranial ultrasounds
used in this study were conducted by a blinded radiology technician as part
of routine screening for neonatal brain abnormalities on day of life 30 ±3.
Post hoc measurements were obtained with electronic calipers using Cen-
tricity Enterprise Web imaging software platform (v3.0.10, GE Healthcare).
Measurements were obtained by a specially trained researcher and were
additionally verified for accuracy and reliability by an experienced radiolo-
gist specialized in neonatal cranial ultrasound reading. The group placement
of each infant remained deidentified.
The following measurements were obtained from each neonatal cranial
ultrasound. In the coronal plane: (i) thickness of the right and left AC in the
mid portion of the superior temporal gyrus, and (ii ) width of the right and
left FHs of the lateral ventricle in the short axis at the level of the foramen of
Monro. In the midsagittal plane: width of the body of the CC. The above
measurements were normalized for each infant based on the TTD (leading
edge to leading edge at the roof of the temporal horns of the lateral ven-
tricles). Sample measurements are shown in Fig. 1.
Data Analysis. SPSS 20 (IBM) was used for all data analyses. Analysis was
focused on determining the effects of sound exposure (i.e., group) on
cortical region of interest related to hearing and language. A multivariate
analysis of variance (MANOVA) was conducted to test for possible differ-
ences in the thickness of the right and left AC (dependent variables) be-
tween the groups (independent variable). An additional MANOVA was
used to compare the width of the right and left FH between the two groups.
Group differences in the width of the CC were examined with a ttest.
Spearman correlation was used to assess the association between gesta-
tional age at birth and brain measures. Within the maternal sounds group,
Spearman correlation was used to assess the association between days of
maternal sound exposure and the brain measures.
ACKNOWLEDGMENTS. We thank the families and babies who participated in
this study; Anna Alkozei and Katie Rand for their kind assistance in early stages of
this work; and Peter Forbes for statistical consultation. This study was supported
in part by grants made to A.L. from the Charles H. Hood Foundation, the Peter
and Elizabeth C. Tower Foundation, Little Giraffe Foundation, Gerber Founda-
tion, and Hailey’s Hope Foundation.
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