Journal of Perinatology www.nature.

com/jp

REVIEW ARTICLE
Methamphetamine: burden, mechanism and impact on
pregnancy, the fetus, and newborn
1,2 ✉ 2
Deepika Sankaran , Satyan Lakshminrusimha and Veena Manja3,4

© The Author(s), under exclusive licence to Springer Nature America, Inc. 2021

While the opioid epidemic has garnered worldwide attention, increasing methamphetamine use has drawn less scrutiny.
Methamphetamine is a highly addictive psychostimulant affecting people from all backgrounds and regions. It is a potent
vasoconstrictor, is associated with arrhythmias and dilated cardiomyopathy. Cardiovascular disease-related mortality is a leading
cause of death in methamphetamine users. Women of childbearing age increasingly use methamphetamine and continue during
pregnancy. In the short term, prenatal methamphetamine use is associated with fetal growth restriction and low birth weight in the
newborn. Animal studies show reduction in uterine and umbilical blood flow following maternal methamphetamine administration.
Based on currently available evidence, prenatal methamphetamine exposure has transient effects on gross motor development, no
effect on language and cognition, and modest effects on behavior and executive functioning with poor inhibitory control, which
may be attributable to early adversity. Further research is needed to evaluate long-term effects of prenatal methamphetamine
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exposure.

Journal of Perinatology (2022) 42:293–299; https://doi.org/10.1038/s41372-021-01271-8

INTRODUCTION substance (Desoxyn) in the United States with an FDA-approved

Prenatal exposure to stimulant drugs, such as methamphetamine,
may adversely impact the developing fetus, especially the central
nervous system [1]. The neurological effects of methampheta-
mines are thought to be due to direct effects on neurotransmitter
release and uptake, and indirect effects on cerebral hemody-
namics including cerebral blood flow, perfusion pressure, and
oxygenation [2]. Our understanding of the effects of metham-
phetamine use during pregnancy has been limited due to small
sample size in published studies and potential confounding from
simultaneous use of other substances of abuse. Recently, the
National Institute on Drug Abuse (NIDA) has supported further
research on this topic [3]. The purpose of this review is to
summarize current knowledge on the effects of methampheta-
mine use during pregnancy and its effects on the pregnant
woman, the fetus, and newborn.
METHAMPHETAMINE ABUSE: A RISING PUBLIC HEALTH CRISIS
Use of synthetic amphetamine derivative methamphetamine ([2 S]-
N-methyl-1-phenyl-propan-2-amine, “meth” or “ice” or “crystal”) is
increasing [4, 5]. Methamphetamine is a psychostimulant that
causes euphoria, intense rush, increased energy and concentration,
decreased appetite, and insomnia. It also increases the risk of
aggression, psychosis, depression, and suicidality [6, 7]. Epidemio-
logical studies demonstrate that amphetamine-type stimulants are
the most widely used illicit drugs in the world after cannabis with
up to 27 million users globally [8]. While the illicit use is widespread,
methamphetamine is also marketed as a Schedule II controlled
indication for obesity and attention deficit hyperactivity disorder
(ADHD) [9]. Nearly two million Americans used methamphetamine
in 2018, an increase of ~400,000 users from 2017; based on latest
data, the prevalence is similar in 2019 [10, 11]. Recent regulations
on the purchase of necessary precursors (such as pseudoephedrine)
for domestic production of methamphetamine led to a distribution
vacuum that was quickly filled by the cartels south of the border. In
2016, 7,542 people died from stimulant overdose including
methamphetamine in the nation, which is a 12-fold increase from
1999 to 2016 [12], and 3-fold between 2011 and 2016 [7]. Overdose
deaths involving methamphetamine almost tripled between 2015
and 2019 [13]. In 2019, 2.3% of the population in North America
aged 15–64 years used methamphetamine [8]. In California,
methamphetamine is a popular drug of misuse and an increasing
cause of death and cardiovascular disease [4]. The amount of
imported methamphetamine that was seized at the national border
has doubled over the past four years [14].
Methamphetamine use has become more prevalent and
popular due to several reasons. It is easy to produce and
inexpensive, it can be synthesized using a one-step process by
reduction of ephedrine or pseudoephedrine, ingredients that were
widely available in the USA in non-prescription allergy medicine
(through methods available on the internet) [15]. Medicaid
beneficiaries account for the majority of methamphetamine-
related hospital visits [16]. It is slow to metabolize resulting in a
high that lasts for 8–24 h, much longer than that from other
common substances of abuse. These factors contribute to the
increasing methamphetamine use among pregnant women,

1
Department of Pediatrics, Adventist Health Rideout Hospital, Marysville, CA, USA. 2Division of Neonatology, Department of Pediatrics, University of California, Davis, CA, USA.
Division of Cardiology, Veterans Affairs Medical Center, Mather, USA. 4Department of Surgery, University of California, Davis, CA, USA. ✉email: dsankaran@ucdavis.edu
3

Received: 23 August 2021 Revised: 27 October 2021 Accepted: 2 November 2021

Published online: 16 November 2021
 D. Sankaran et al.
294
Fig. 1 Mechanisms of action of methamphetamine. Illustration depicting the various mechanisms by which methamphetamine (MA)
increases the dopamine (D), norepinephrine (NE), and serotonin (5HT) concentrations in the synapses within the central nervous system. MAO
monoamine-oxidase, TH tyrosine hydroxylase. Copyright Satyan Lakshminrusimha.
across all socioeconomic strata [13]. Higher rates of testing likely
result in a higher ascertainment rate in women from lower
socioeconomic status. Women in the reproductive age group may
start using methamphetamine for various reasons, ranging from
appetite suppression to lose weight, to cope with stress.
Methamphetamine use during pregnancy has increased over the
past 30 years in the USA, with estimated prevalence ranging
between 0.7–5% in endemic areas [17, 18]. Furthermore,
methamphetamine causes fewer fatal overdoses than opioids,
but more long-term medical, psychiatric, and societal problems
[19, 20]. Substantial percentage of syphilis transmission has been
reported among methamphetamine users [21]. This compounds
the public health crisis with likely added risk of maternal perinatal
syphilis and congenital syphilis in the newborn [21]. The effects of
methamphetamine abuse are likely worse compared to prescribed
amphetamine use due to maternal and fetal exposure to higher
doses, more frequent use, poly-substance use, maternal malnutri-
tion, and adverse social circumstances. Currently, there are no
approved medications for the treatment of methamphetamine-
use disorder; Bupropion and Naltrexone have shown some
promising results [22, 23].
MECHANISM OF ACTION OF METHAMPHETAMINE (FIG. 1)
Methamphetamine acts on the central nervous system as a
psychostimulant through a non-exocytotic mechanism, causing
the release of monoamine neurotransmitters, including dopamine,
norepinephrine, and serotonin [24]. The mechanisms of actions
(Fig. 1) include the following:
a. Increasing the cytosolic levels of monoamines by redistribu-
tion from synaptic vesicles to the cytosol [25]
b. Reverse transport of neurotransmitters through plasma
membrane transporters [26].
c. Blocking the activity of monoamine transporters (similar to
cocaine) [27].
d. Decreasing expression of dopamine transporters at cell
surface [28].
e. Inhibiting monoamine oxidase, methamphetamine
increases cytosolic levels of monoamines [29].
f. Increasing the activity and expression of the dopamine
synthesizing enzyme tyrosine hydroxylase [15, 30].
Methamphetamine and other amphetamines act as highly
potent releasers of monoamines, with longer elimination half-life
[31] than many other psychostimulants (8–13 h for methamphe-
tamine [31] vs. 1–3 h for cocaine) leading to longer sustained
effects. Owing to high lipid solubility, methamphetamine crosses
the blood–brain barrier rapidly [32]. Secondary to monoamine
release, the acute effects include feelings of euphoria, intense
rush, feeling of well-being, alertness, increased libido, and
decreased appetite. Somatic effects from the release of epinephr-
ine and norepinephrine by adrenal glands may include increased
blood pressure, hyperthermia, stroke, arrhythmias, tremors; acute
psychological effects include anxiety, memory impairment [33],
insomnia, aggression, paranoia, and hallucinations. Additionally,
acute neurotoxicity can be due to enhanced susceptibility to
oxidative stress from production of reactive oxygen species (along
with dysfunction of mitochondrial metabolism and promoting
apoptotic neuronal death) [34–37], excitotoxicity [38], and
neuroinflammation due to microglial activation and pro-
inflammatory cytokine release [39, 40].
Long-term effects are secondary to impaired expression of
tyrosine and tyrosine hydroxylase, monoamine transporters,
dopamine depletion, decreased density of dopamine D2 receptors
(with recovery of receptor numbers following abstinence), and
neurodegeneration [41]. Moreover, methamphetamine use has
been associated with structural abnormalities in the brain such as
Journal of Perinatology (2022) 42:293 – 299
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295

Fig. 2 Graphical abstract on effects of prenatal methamphetamine use on maternal, fetal, neonatal and neurodevelopmental outcomes.
Methamphetamine can be synthesized by inexpensive methods in “Meth labs”. Methamphetamine causes a monoamine transmitter surge
that in turn causes acute vasospasm with resultant maternal cardiovascular and placental complications. Respiratory depression
and echodensities on head ultrasound have been reported in newborns. Long-term neurodevelopmental outcomes are variable with some
reports of normal gross motor and language development but impaired behavioral and emotional control and decreased executive
functioning. Copyright Satyan Lakshminrusimha.

smaller volume of temporal lobe [42] and smaller gray matter
volume (accompanied by larger white matter volume) particularly
in cingulate, limbic, and paralimbic cortices, striatum and
hippocampus [43, 44]. Methamphetamine abusers experience
lower levels of dopamine transporters in striatum [45–47] and
prefrontal cortex [48], and differences in cerebral regional glucose
metabolism [47, 49]. Age-related loss of cortical gray matter in
stimulant abusers may be associated with reduced ability to
experience euphoric effects and decrease in addiction with
advancing age.
The effects of methamphetamine on the cardiovascular system
include the following: [4, 50, 51]
a. Acute vasoconstriction and vasospasm, endothelial damage,
pulmonary hypertension, and heart failure.
b. Enhanced atherosclerotic plaque formation: due to
enhanced inflammation from endothelial activation,
increased T-cell and macrophage driven pro-inflammatory
signaling.
c. Cardiac structural and electrical remodeling (fibrosis, inflam-
mation), QT prolongation, and susceptibility to arrhythmias.
d. Mitochondrial dysfunction and dilated cardiomyopathy.
flow) [56]. Furthermore, methamphetamine use can cause acute
vasospasm, atherosclerotic disease, structural and electrical
remodeling of cardiac tissue leading to arrhythmias, heart failure,
and pulmonary hypertension [4]. In the setting of preexisting
preeclampsia, methamphetamine use may precipitate hyperten-
sive crisis. Reduced gestational weight gain has also been
reported [57].
Serotonin and norepinephrine transporters are expressed
abundantly in the placenta. They are thought to play an important
role in homeostasis of the amniotic fluid and vasoconstriction of
the placental vascular bed. Through these transporters, metham-
phetamines may contribute to the development of preeclampsia
[58], fetal growth restriction [18], placental hemorrhages including
abruption [59], and preterm labor [60]. Amphetamine concentra-
tions are 3–7 times higher in breast milk compared to maternal
plasma, indicating its concentration in breast milk [61].
Early pregnancy losses (combination of miscarriages and
medical terminations) have been reported among 33–41% of
pregnant methamphetamine users when compared to ~10–15%
in general pregnant population [62, 63]. A systematic review and
meta-analysis of retrospective case–control studies reported no
increase in maternal pregnancy-related complications [64]. There
is very low certainty in this result due to limited data and
substantial heterogeneity among included studies.

EFFECTS ON PREGNANCY
The stimulant effects of methamphetamine on pregnant women
could potentially endanger the outcomes for the mother and her
fetus (Fig. 2). During normal pregnancy, there is 30–50% increase
in cardiac output with slight decrease in systemic vascular
resistance and blood pressure (BP) [52, 53]. Animal studies have
shown higher maternal BP and heart rates with methampheta-
mine intravenous (IV) bolus administration during pregnancy
(Table S1, supplement) [54, 55]. Burchfield et al. observed a brief
episode of bradycardia followed by prolonged tachycardia, and
54–63% increase in BP after IV administration of methampheta-
mine in pregnant sheep [54]. They also observed fetal hypoxemia,
likely secondary to reduced placental perfusion (due to increased
uterine vascular resistance, decreased uterine and umbilical blood
EFFECTS ON THE FETUS
In the late 20th and early 21st century, several animal studies
evaluated the maternal-fetal effects of maternal methampheta-
mine administration prior to delivery (Table S1, supplement)
[54, 65, 66]. Burchfield et al. demonstrated that methamphetamine
crossed the placenta within 30 seconds of IV administration in the
ewe [54]. Longer elimination half-life led to high fetal tissue
concentrations of methamphetamine in the placenta, lung,
intestine, kidney, liver, brain, and heart, which were higher than
the plasma concentrations, within 2.5 min after maternal admin-
istration [54, 67]. Stek et al. evaluated the effect of incremental IV
dose of methamphetamine (0.03, 0.1, 0.3 and 1 mg/kg for the ewe
and 0.03, 0.1, 0.3, 1 and 3 mg/kg for the lamb) on maternal and

Journal of Perinatology (2022) 42:293 – 299

 D. Sankaran et al.
296
fetal PaO2, pH and hemodynamic parameters [56]. In addition to
dose-dependent increase in maternal BP and uterine vascular
resistance, the authors reported increase in fetal heart rate while
there was a decrease in uterine blood flow and fetal PaO2 [56].
Fetal methamphetamine injection resulted in dose-related
increase in fetal BP and umbilical blood flow along with significant
decrease in fetal pH [56]. Such sudden fluctuations and dose-
related increases in fetal BP has the potential to alter cerebral
blood flow resulting in overdistension and rupture of cerebral
blood vessels (due to limited ability of the fetus to autoregulate
the cerebral blood flow), and may predispose to intraventricular
hemorrhage. Won et al., demonstrated methamphetamine con-
centration of 122 ± 6 ng/mg protein and amphetamine concen-
tration of 18 ± 2 ng/mg protein in fetal mouse brain after a single
subcutaneous injection of 40 mg/kg methamphetamine to the
pregnant dams [68].
Prenatal methamphetamine use is associated with fetal growth
restriction [69–71]. A case series of eight fetal and infant deaths
was reported by Stewart et al., where maternal methamphetamine
use was listed as a contributing factor for death; median
gestational age among fetal deaths was 30 weeks (range 20-36
weeks), and two out of eight were stillborn at term gestation [72].
EFFECTS ON THE NEWBORN
Profound effects on neurodevelopment and behavior outcomes
were observed in neonatal rats after prenatal and postnatal
methamphetamine exposure [73–76]. Impairment of postural
motor movements during the first three weeks after birth [65]
and delayed habituation in a novel environment were also
observed in rat pups (Table S1, supplement) [77]. In 1963,
Sussman reported respiratory distress in a newborn born to a
mother with methamphetamine habituation [78]. We speculate
that neonatal withdrawal from the stimulant effects of metham-
phetamine after separation from mother by clamping of the
umbilical cord, may cause respiratory depression in the newborn.
One hundred and four mother-infant dyads with positive urine
toxicology screen results at the time of delivery were studied
retrospectively by Oro et al., and they reported that methamphe-
tamine and cocaine-exposed neonates had lower birth weight
[18], smaller head circumferences [79], and were more likely to be
small for gestational age [80, 81] and premature [82] compared to
drug-free comparison group (Table S1, supplement) [83]. Little
et al., corroborated these findings, and additionally reported a
decrease in newborn length [84]. In the systematic review and
meta-analysis by Kalaitzopoulos et al., lower gestational age at
birth, birth weight, head circumference, body length, and Apgar
score were identified among newborns born after prenatal
methamphetamine exposure compared to control non-exposed
newborns [64].
A retrospective study by Smith et al. compared 134 exposed
and 160 non-exposed neonates and found that 49% of the
exposed neonates had symptoms of withdrawal with 4% requiring
treatment [70]. There have been rare reports of association of
dexamphetamine use in the first trimester with increased
frequency of congenital anomalies including congenital heart
diseases [85, 86]. However, the “Collaborative Perinatal Project”
showed no increased frequency of congenital anomalies in 215
infants with prenatal methamphetamine-exposure (including 89
with first trimester exposure) [87]. There are no studies evaluating
cardiovascular effects of prenatal methamphetamine exposure on
the neonates in short and long term, except for an ongoing
prospective observational study (NCT04616625) [88].
Seemingly normal term newborns born to mothers using
methamphetamine during pregnancy studied retrospectively
were found to have abnormal findings on cranial ultrasound
(35% of drug-exposed infants compared to only 5% of normal
infants), including intraventricular hemorrhage, echodensities
known to be linked to necrosis, and cavitary lesions (predomi-
nantly in basal ganglia, frontal lobes, and posterior fossa) [89].
Severe neurologic and hepatic toxicity was reported in a newborn
prenatally exposed to methamphetamine [90]. Furthermore,
prenatal exposure to methamphetamine increases the odds of
neonatal death and infant death [59].
LONG TERM EFFECTS ON CHILDREN
Chang et al. observed abnormal brain metabolite concentrations
in frontal white matter and thalamus (due to increased axonal
density from increased dendritic branching) and poor perfor-
mance on visual motor integration in children exposed to
methamphetamine in utero [91]. The authors speculate acceler-
ated but aberrant neuronal and glial development in these
children. Emerging evidence links long-term neurodevelopmental
and behavioral outcomes to prenatal methamphetamine expo-
sure [92–100]. NIDA- funded large prospective cohort studies
compared neuro-behavioral outcomes during infancy and child-
hood between methamphetamine-exposed and unexposed
cohorts. Three- and five-year neurodevelopmental follow-up
revealed that methamphetamine exposed children were emo-
tionally reactive, anxious/ depressed, and were at risk for ADHD
and, with 7.5-year follow-up, children had increased early
adversity index score, increased externalizing, rule-breaking
behavior, and aggressive behavior (Table S1, supplement)
[97, 101, 102]. Methamphetamine acts on the pre-frontal cortex
[103] affecting memory, behavior, and cognition, resulting in poor
inhibitory control and impaired executive function in prenatally
exposed children [92–95, 98, 102]. Epigenetic effects and
methamphetamine-induced oxidative stress leading to shifting
neuronal phenotype and behavioral alterations have been
reported as well [104]. In a prospective pilot study, decreased
volume of caudate, putamen, globus pallidus, and hippocampus
in magnetic resonance imaging correlated with deficits in
sustained attention and verbal memory that may contribute to
poorer learning [105].
A review of outcomes from the multi-site Infant Development
Environment and Lifestyle (IDEAL) study showed no effect on
gross motor, receptive and expressive language, or mental
development at 3 years, but significant effects on behavioral
and emotional control and executive functioning [93]. Although
the study was limited by maternal self-reported methampheta-
mine use, the IDEAL study used multivariate statistical techniques
to account for co-exposure to alcohol, tobacco, and marijuana.
When interpreted in the context of home environment and
primary caregiver characteristics, the childhood neurodevelop-
mental outcomes in prenatally exposed children were likely
attributed to early adversity.
The American College of Obstetricians and Gynecologists
suggest continued surveillance for children born after prenatal
methamphetamine exposure due to its potential neurodevelop-
mental effects [106]. Many children born to methamphetamine-
users may undergo child protective services involvement and
foster care placement due to unstable parental living circum-
stances [107, 108]. Adverse social environment during their early
life and neglect may significantly impact the overall growth and
development of these children [109–111].
CONCLUSIONS
The methamphetamine epidemic continues to be relatively under-
recognized by legislators and the media [12]. Availability of highly
addictive, relatively inexpensive methamphetamine to women of
child-bearing age may facilitate its use, potentially leading to
effects on somatic growth and fetal neurotoxicity from prenatal
exposure [92–95]. More research is needed to fully understand
its effects on the developing fetus and resulting adverse
Journal of Perinatology (2022) 42:293 – 299

neurodevelopmental and cardiovascular outcomes, especially in
the context of early adversity and environmental influences. Based
on currently available evidence, prenatal methamphetamine
exposure has transient effects on gross motor development, no
effect on language and cognition, and modest effects on behavior
and executive functioning with poor inhibitory control, which may
be attributable to early adversity. There are no studies evaluating
the cardiovascular effects on the child after prenatal metham-
phetamine exposure.
Pregnancy may be a window of opportunity to intervene,
provide necessary medical care and psychosocial support to
methamphetamine users. Increasing public awareness of adverse
effects of methamphetamine especially in high-risk communities
is necessary to increase funding to implement measures to curb
its use and limit its effects on pregnant women and their children.
REFERENCES
1. Dixon SD, Bejar R. Echoencephalographic findings in neonates associated with
maternal cocaine and methamphetamine use: Incidence and clinical correlates.
J Pediatrics. 1989;115:770–778. https://doi.org/10.1016/S0022-3476(89)80661-4
2. Dixon SD. Effects of transplacental exposure to cocaine and methamphetamine
on the neonate. West J Med. 1989;150:436.
3. NIDA. What are the risks of methamphetamine misuse during pregnancy?. National
Institute on Drug Abuse website. https://www.drugabuse.gov/publications/
research-reports/methamphetamine/what-are-risks-methamphetamine-misuse-
during-pregnancy. April 13, 2021 Accessed September 30, 2021.
4. Kevil CG, Goeders NE, Woolard MD, Bhuiyan MS, Dominic P, Kolluru GK, et al.
Methamphetamine Use and Cardiovascular Disease. Arteriosclerosis, thrombo-
sis, Vasc Biol. 2019;39:1739–46. https://doi.org/10.1161/atvbaha.119.312461
5. Stoneberg DM, Shukla RK, Magness MB. Global methamphetamine trends: an
evolving problem. Int Crim justice Rev. 2018;28:136–61.
6. McKetin R, Leung J, Stockings E, Huo Y, Foulds J, Lappin JM, et al. Mental health
outcomes associated with of the use of amphetamines: A systematic review and
meta-analysis. EClinicalMedicine. 2019;16:81–97. https://doi.org/10.1016/j.
eclinm.2019.09.014
7. Richards JR, Hamidi S, Grant CD, Wang CG, Tabish N, Turnipseed SD, et al.
Methamphetamine use and emergency department utilization: 20 years later. J
Addict. 2017;2017:4050932–4050932. https://doi.org/10.1155/2017/4050932
8. UNODC. World Drug Report 2020. United Nations Office on Drugs and Crime;
https://wdr.unodc.org/wdr2020/field/WDR20_Booklet_2.pdf, 18- 25 (2020).
9. Hendricks EJ. Off-label drugs for weight management. Diabetes Metab Syndr
Obes. 2017;10:223–34. https://doi.org/10.2147/DMSO.S95299
10. Elinore F. McCance-Katz, M, PhD. Substance Abuse and Mental Health Services
Administration. The National Survery on Drug Use and Health: 2018. https://
www.samhsa.gov/data/sites/default/files/cbhsq-reports/Assistant-Secretary-
nsduh2018_presentation.pdf, 36-37 (2018).
11. Administration., SAAMHS Key substance use and mental health indicators in the
United States: Results from the 2019 National Survey on Drug Use and Health
(HHS Publication No. PEP20-07-01-001, NSDUH Series H-55). Rockville, MD:
Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental
Health Services Administration. Retrieved from https://www.samhsa.gov/data/.
(2020).
12. Artigiani EE, Hsu MH, McCandlish D, and Wish ED Methamphetamine: a Regional
Drug Crisis. National Drug Early Warning System 2018 https://cesar.umd.edu/
sites/cesar.umd.edu/files/pubs/ndews-scs-methamphetamine-report-
september-2018-final.pdf, 2–6 (2018).
13. Han B, Compton WM, Jones CM, Einstein EB & Volkow, ND Methamphetamine
Use, Methamphetamine Use Disorder, and Associated Overdose Deaths Among
US Adults. JAMA Psychiatry. https://doi.org/10.1001/jamapsychiatry.2021.2588
(2021).
14. Customs US, P. B. CBP enforcement statistics FY 2021. US Department of
Homeland Security, Washington, DC. https://www.cbp.gov/newsroom/stats/
drug-seizure-statistics (2021).
15. Sulzer D, Sonders MS, Poulsen NW, Galli A. Mechanisms of neurotransmitter
release by amphetamines: a review. Prog Neurobiol. 2005;75:406–33. https://doi.
org/10.1016/j.pneurobio.2005.04.003
16. Winkelman TNA, Admon LK, Jennings L, Shippee ND, Richardson CR, Bart G.
Evaluation of Amphetamine-Related Hospitalizations and Associated Clinical
Outcomes and Costs in the United States. JAMA Netw Open. 2018;1:
e183758–e183758. https://doi.org/10.1001/jamanetworkopen.2018.3758
17. Derauf C, LaGasse LL, Smith LM, Grant P, Shah R, Arria A, et al. Demographic and
psychosocial characteristics of mothers using methamphetamine during
Journal of Perinatology (2022) 42:293 – 299
D. Sankaran et al.
297
pregnancy: preliminary results of the infant development, environment, and
lifestyle study (IDEAL). Am J Drug Alcohol Abus. 2007;33:281–289. https://doi.
org/10.1080/00952990601175029
18. Wright TE, Schuetter R, Tellei J, Sauvage L. Methamphetamines and pregnancy
outcomes. J addiction Med. 2015;9:111–117. https://doi.org/10.1097/ADM.00000
00000000101
19. Mattson CL, Tanz LJ, Quinn K, Kariisa M, Patel P, Davis NL. Trends and geo-
graphic patterns in drug and synthetic opioid overdose deaths - United States,
2013-2019. MMWR Morb Mortal Wkly Rep. 2021;70:202–207. https://doi.org/
10.15585/mmwr.mm7006a4
20. Chiang M, Lombardi D, Du J, Makrum U, Sitthichai R, Harrington A, et al.
Methamphetamine-associated psychosis: clinical presentation, biological basis,
and treatment options. Hum Psychopharmacol. 2019;34:e2710 https://doi.org/
10.1002/hup.2710
21. Kidd SE, Grey JA, Torrone EA, Weinstock HS. Increased methamphetamine,
injection drug, and heroin use among women and heterosexual men with
primary and secondary syphilis - United States, 2013–2017. MMWR Morb Mortal
Wkly Rep. 2019;68:144–148. https://doi.org/10.15585/mmwr.mm6806a4
22. Ashok AH, Mizuno Y, Volkow ND, Howes OD. Association of stimulant use with
dopaminergic alterations in users of cocaine, amphetamine, or methampheta-
mine: a systematic review and meta-analysis. JAMA Psychiatry. 2017;74:511–519.
https://doi.org/10.1001/jamapsychiatry.2017.0135
23. Trivedi MH, Walker R, Ling W, dela Cruz A, Sharma G, Carmody T, et al.
Bupropion and naltrexone in methamphetamine use disorder. N. Engl J Med.
2021;384:140–153. https://doi.org/10.1056/NEJMoa2020214
24. Perez FA, Blythe S, Wouldes T, McNamara K, Black KI, Oei JL. Prenatal
methamphetamine-impact on the mother and child-a review. Addiction. 2021.
https://doi.org/10.1111/add.15509
25. Brown JM, Hanson GR, Fleckenstein AE. Regulation of the vesicular monoamine
transporter-2: a novel mechanism for cocaine and other psychostimulants. J
Pharmacol Exp therapeutics. 2001;296:762–767.
26. Khoshbouei H, Wang H, Lechleiter JD, Javitch JA, Galli A. Amphetamine-induced
dopamine efflux. A voltage-sensitive and intracellular Na+-dependent
mechanism. J Biol Chem. 2003;278:12070–12077. https://doi.org/10.1074/jbc.
M212815200
27. Schmitz Y, Lee CJ, Schmauss C, Gonon F, Sulzer D. Amphetamine distorts
stimulation-dependent dopamine overflow: effects on D2 autoreceptors,
transporters, and synaptic vesicle stores. J Neurosci: Off J Soc Neurosci.
2001;21:5916–5924.
28. Saunders C, Ferrer JV, Shi L, Chen J, Merrill G, Lamb ME, et al. Amphetamine-
induced loss of human dopamine transporter activity: an internalization-
dependent and cocaine-sensitive mechanism. Proc Natl Acad Sci USA.
2000;97:6850–6855. https://doi.org/10.1073/pnas.110035297
29. Mantle TJ, Tipton KF, Garrett NJ. Inhibition of monoamine oxidase by amphe-
tamine and related compounds. Biochemical Pharmacol. 1976;25:2073–2077.
https://doi.org/10.1016/0006-2952(76)90432-9
30. Mandell AJ, Morgan M. Amphetamine induced increase in tyrosine hydroxylase
activity. Nature. 1970;227:75–76. https://doi.org/10.1038/227075a0
31. Cruickshank CC, Dyer KR. A review of the clinical pharmacology of metham-
phetamine. Addiction. 2009;104:1085–1099. https://doi.org/10.1111/j.1360-
0443.2009.02564.x
32. Barr AM, Panenka WJ, MacEwan GW, Thornton AE, Lang DJ, Honer WG, et al. The
need for speed: an update on methamphetamine. addiction J psychiatry Neu-
rosci: JPN. 2006;31:301–313.
33. Simon SL, Carnell J, Brethen P, Rawson R, Ling W. Cognitive impairment in
individuals currently using methamphetamine. Am J Addictions.
2000;9:222–231.
34. Cadet JL, Brannock C. Free radicals and the pathobiology of brain dopamine
systems. Neurochem Int. 1998;32:117–131. https://doi.org/10.1016/s0197-0186
(97)00031-4
35. Shin EJ, Tran HQ, Nguyen PT, Jeong JH, Nah SY, Jang CG, et al. Role of mito-
chondria in methamphetamine-induced dopaminergic neurotoxicity: involve-
ment in oxidative stress, neuroinflammation, and pro-apoptosis-a review.
Neurochem Res. 2018;43:66–78. https://doi.org/10.1007/s11064-017-2318-5
36. Lin M, Chandramani-Shivalingappa P, Jin H, Ghosh A, Anantharam V, Ali S, et al.
Methamphetamine-induced neurotoxicity linked to ubiquitin-proteasome sys-
tem dysfunction and autophagy-related changes that can be modulated by
protein kinase C delta in dopaminergic neuronal cells. Neuroscience.
2012;210:308–332. https://doi.org/10.1016/j.neuroscience.2012.03.004
37. Raineri M, Gonzalez B, Goitia B, Garcia-Rill E, Krasnova IN, Cadet JL, et al.
Modafinil abrogates methamphetamine-induced neuroinflammation and
apoptotic effects in the mouse striatum. PLoS One. 2012;7:e46599 https://doi.
org/10.1371/journal.pone.0046599
38. Moratalla R, Khairnar A, Simola N, Granado N, García-Montes JR, Porceddu PF,
et al. Amphetamine-related drugs neurotoxicity in humans and in experimental
 D. Sankaran et al.
298
animals: Main mechanisms. Prog Neurobiol. 2017;155:149–170. https://doi.org/
10.1016/j.pneurobio.2015.09.011
39. Xu E, Liu J, Liu H, Wang X, Xiong H. Role of microglia in methamphetamine-
induced neurotoxicity. Int J Physiol Pathophysiol Pharm. 2017;9:84–100.
40. Shah A, Silverstein PS, Singh DP, Kumar A. Involvement of metabotropic glu-
tamate receptor 5, AKT/PI3K signaling and NF-κB pathway in
methamphetamine-mediated increase in IL-6 and IL-8 expression in astrocytes. J
Neuroinflammation. 2012;9:52 https://doi.org/10.1186/1742-2094-9-52
41. Yang X, Wang Y, Li Q, Zhong Y, Chen L, Du Y, et al. The Main Molecular
Mechanisms Underlying Methamphetamine- Induced Neurotoxicity and Impli-
cations for Pharmacological Treatment. Front Mol Neurosci. 2018;11:186–186.
https://doi.org/10.3389/fnmol.2018.00186
42. Bartzokis G, Beckson M, Lu PH, Edwards N, Rapoport R, Wiseman E, et al. Age-
related brain volume reductions in amphetamine and cocaine addicts and
normal controls: implications for addiction research. Psychiatry Res: Neuroima-
ging. 2000;98:93–102.
43. Bartzokis G, Beckson M, Lu PH, Nuechterlein KH, Edwards N, Mintz J. Age-related
changes in frontal and temporal lobe volumes in men: a magnetic resonance
imaging study. Arch Gen Psychiatry. 2001;58:461–465. https://doi.org/10.1001/
archpsyc.58.5.461
44. Thompson PM, Hayashi KM, Simon SL, Geaga JA, Hong MS, Sui Y, et al. Structural
abnormalities in the brains of human subjects who use methamphetamine. J
Neurosci. 2004;24:6028–6036.
45. McCann UD, Wong DF, Yokoi F, Villemagne V, Dannals RF, Ricaurte GA. Reduced
striatal dopamine transporter density in abstinent methamphetamine and
methcathinone users: evidence from positron emission tomography studies
with [11C] WIN-35,428. J Neurosci. 1998;18:8417–8422.
46. Sekine Y, Iyo M, Ouchi Y, Matsunaga T, Tsukada H, Okada H, et al.
Methamphetamine-related psychiatric symptoms and reduced brain dopamine
transporters studied with PET. Am J Psychiatry. 2001;158:1206–1214.
47. Volkow ND, Chang L, Wang G-J, Fowler JS, Leonido-Yee M, Franceschi D, et al.
Association of dopamine transporter reduction with psychomotor impairment
in methamphetamine abusers. Am J Psychiatry. 2001;158:377–382.
48. Sekine Y, Minabe Y, Ouchi Y, Takei N, Iyo M, Nakamura K, et al. Association of
dopamine transporter loss in the orbitofrontal and dorsolateral prefrontal cor-
tices with methamphetamine-related psychiatric symptoms. Am J Psychiatry.
2003;160:1699–1701.
49. London E, Simon S, Berman S, Mandelkern M, Lichtman A, Bramen J, et al.
Regional cerebral dysfunction associated with mood disturbances in abstinent
methamphetamine abusers. Arch Gen Psychiatry. 2004;61:73–84.
50. Richards JR, Harms BN, Kelly A, Turnipseed SD. Methamphetamine use and heart
failure: prevalence, risk factors, and predictors. Am J Emerg Med.
2018;36:1423–1428. https://doi.org/10.1016/j.ajem.2018.01.001
51. Maeno Y, Iwasa M, Inoue H, Koyama H, Matoba R. Methamphetamine induces
an increase in cell size and reorganization of myofibrils in cultured adult rat
cardiomyocytes. Int J Leg Med. 2000;113:201–207.
52. Metcalfe J, Ueland K. Maternal cardiovascular adjustments to pregnancy. Prog
Cardiovasc Dis. 1974;16:363–374. https://doi.org/10.1016/0033-0620(74)90028-0
53. Ueland K, Novy MJ, Peterson EN, Metcalfe J. Maternal cardiovascular dynamics.
IV. The influence of gestational age on the maternal cardiovascular response to
posture and exercise. Am J Obstet Gynecol. 1969;104:856–864.
54. Burchfield DJ, Lucas VW, Abrams RM, Miller RL, DeVane CL. Disposition and
pharmacodynamics of methamphetamine in pregnant sheep. Jama.
1991;265:1968–1973. https://doi.org/10.1001/jama.1991.03460150072026
55. Stek AM, Fisher BK, Baker RS, Lang U, Tseng C-Y, Clark KE. Maternal and fetal
cardiovascular responses to methamphetamine in the pregnant sheep. Am J
Obstet Gynecol. 1993;169:888–897.
56. Stek AM, Scott Baker R, Fisher BK, Lang U, Clark KE. Fetal responses to maternal
and fetal methamphetamine administration in sheep. Am J Obstet Gynecol.
1995;173:1592–1598. https://doi.org/10.1016/0002-9378(95)90654-1
57. Acuff-Smith KD, Schilling MA, Fisher JE, Vorhees CV. Stage-specific effects of
prenatal d-methamphetamine exposure on behavioral and eye development in
rats. Neurotoxicology Teratol. 1996;18:199–215. https://doi.org/10.1016/0892-
0362(95)02015-2
58. Bottalico B, Larsson I, Brodszki J, Hernandez-Andrade E, Casslen B, Marsal K, et al.
Norepinephrine transporter (NET), serotonin transporter (SERT), vesicular
monoamine transporter (VMAT2) and organic cation transporters (OCT1, 2 and
EMT) in human. Placenta pre-eclamptic normotensive pregnancies Placenta.
2004;25:518–529. https://doi.org/10.1016/j.placenta.2003.10.017
59. Gorman MC, Orme KS, Nguyen NT, Kent EJ, Caughey AB. Outcomes in preg-
nancies complicated by methamphetamine use. Am J Obstet Gynecol.
2014;211:429.e421–-429.e427. https://doi.org/10.1016/j.ajog.2014.06.005
60. Ganapathy V. Drugs of abuse and human placenta. Life Sci. 2011;88:926–930.
https://doi.org/10.1016/j.lfs.2010.09.015
61. Steiner E, Villén T, Hallberg M, Rane A. Amphetamine secretion in breast milk.
Eur J Clin Pharm. 1984;27:123–124.
62. Brecht M-L, Herbeck DM. Pregnancy and fetal loss reported by
methamphetamine-using women. Subst Abus. 2014;8:25–33. https://doi.org/
10.4137/SART.S14125
63. Abdul-Khabir W, Hall T, Swanson AN, Shoptaw S. Intimate partner violence and
reproductive health among methamphetamine-using women in los angeles: a
qualitative pilot study. J Psychoact Drugs. 2014;46:310–316. https://doi.org/
10.1080/02791072.2014.934978
64. Kalaitzopoulos D-R, Chatzistergiou K, Amylidi A-L, Kokkinidis DG, Goulis DG.
Effect of methamphetamine hydrochloride on pregnancy outcome: a systematic
review and meta-analysis. J Addiction Med. 2018;12:220–226. https://doi.org/
10.1097/adm.0000000000000391
65. Šlamberová R, Pometlová M, Charousová P. Postnatal development of rat pups
is altered by prenatal methamphetamine exposure. Prog Neuro-
Psychopharmacol Biol Psychiatry. 2006;30:82–88. https://doi.org/10.1016/j.
pnpbp.2005.06.006
66. Šlamberová R, Yamamotová A, Schutová B, Hrubá L, Pometlová M. Impact of
prenatal methamphetamine exposure on the sensitivity to the same drug in
adult male rats. Prague Med Rep. 2011;112:102–114.
67. Garcia-Bournissen F, Rokach B, Karaskov T, Koren G. Methamphetamine
detection in maternal and neonatal hair: implications for fetal safety. Arch Dis
Child - Fetal Neonatal Ed. 2007;92:351–355. https://doi.org/10.1136/
adc.2006.100156
68. Won L, Bubula N, McCoy H, Heller A. Methamphetamine concentrations in fetal
and maternal brain following prenatal exposure. Neurotoxicology Teratol.
2001;23:349–354.
69. Eriksson M, Jonsson B, Steneroth G, Zetterstrom R. Cross-sectional growth of
children whose mothers abused amphetamines during pregnancy. Acta Pae-
diatr. 1994;83:612–617. https://doi.org/10.1111/j.1651-2227.1994.tb13091.x
70. Smith L, Yonekura ML, Wallace T, Berman N, Kuo J, Berkowitz C. Effects of
prenatal methamphetamine exposure on fetal growth and drug withdrawal
symptoms in infants born at term. J Dev Behav Pediatr. 2003;24:17–23. https://
doi.org/10.1097/00004703-200302000-00006
71. Chomchai C, Manorom N, Watanarungsan P, Yossuck P, Chomchai S. Metham-
phetamine abuse during pregnancy and its health impact on neonates born at
Siriraj Hospital, Bangkok, Thailand. Southeast Asian J tropical Med public health.
2004;35:228–231.
72. Stewart JL, Meeker JE. Fetal and infant deaths associated with maternal
methamphetamine abuse. J Anal Toxicol. 1997;21:515–517. https://doi.org/
10.1093/jat/21.6.515
73. McDonnell-Dowling K, Donlon M, Kelly JP. Methamphetamine exposure during
pregnancy at pharmacological doses produces neurodevelopmental and
behavioural effects in rat offspring. Int J Developmental Neurosci.
2014;35:42–51. https://doi.org/10.1016/j.ijdevneu.2014.03.005
74. Vorhees CV, Skelton MR, Grace CE, Schaefer TL, Graham DL, Braun AA, et al.
Effects of (+)-methamphetamine on path integration and spatial learning, but
not locomotor activity or acoustic startle, align with the stress hyporesponsive
period in rats. Int J Developmental Neurosci. 2009;27:289–298. https://doi.org/
10.1016/j.ijdevneu.2008.12.003
75. Smith LM, LaGasse LL, Derauf C, Grant P, Shah R, Arria A, et al. Prenatal
methamphetamine use and neonatal neurobehavioral outcome. Neurotoxicol-
ogy Teratol. 2008;30:20–28.
76. Smith LM, LaGasse LL, Derauf C, Newman E, Shah R, Haning W, et al. Motor and
cognitive outcomes through three years of age in children exposed to prenatal
methamphetamine. Neurotoxicol Teratol. 2011;33:176–184. https://doi.org/
10.1016/j.ntt.2010.10.004
77. Thompson VB, Heiman J, Chambers JB, Benoit SC, Buesing WR, Norman MK,
et al. Long-term behavioral consequences of prenatal MDMA exposure. Physiol
Behav. 2009;96:593–601.
78. Sussman S. Narcotic and methamphetamine use during pregnancy. Eff newborn
infants Am J Dis Child. 1963;106:325–330. https://doi.org/10.1001/
archpedi.1963.02080050327013
79. Shah R, Diaz SD, Arria A, LaGasse LL, Derauf C, Newman E, et al. Prenatal
methamphetamine exposure and short-term maternal and infant medical out-
comes. Am J Perinatol. 2012;29:391–400.
80. Smith LM, LaGasse LL, Derauf C, Grant P, Shah R, Arria A, et al. The infant
development, environment, and lifestyle study: effects of prenatal metham-
phetamine exposure, polydrug exposure, and poverty on intrauterine growth.
Pediatrics. 2006;118:1149–1156.
81. Nguyen D, Smith LM, LaGasse LL, Derauf C, Grant P, Shah R, et al. Intrauterine
growth of infants exposed to prenatal methamphetamine: results from the
infant development, environment, and lifestyle study. J pediatrics.
2010;157:337–339.
Journal of Perinatology (2022) 42:293 – 299

82. Gargari, SS, Fallahian, M, Haghighi, L, Hosseinnezhad-Yazdi, M, Dashti, E &
Dolan, K. Maternal and neonatal complications of substance abuse in Iranian
pregnant women. Acta Med Iran. 2012;50:411–16.
83. Oro AS, Dixon SD. Perinatal cocaine and methamphetamine exposure: maternal
and neonatal correlates. J pediatrics. 1987;111:571–578.
84. Little BB, Snell LM, Gilstrap L 3rd. Methamphetamine abuse during pregnancy:
outcome and fetal effects. Obstet Gynecol. 1988;72:541–544.
85. Nelson MM, Forfar JO. Associations between drugs administered during preg-
nancy and congenital abnormalities of the fetus. Br Med J. 1971;1:523–527.
86. Nora J, Vargo T, Nora A, Love K, Mcnamara D. Dexamphetamine: a possible
environmental trigger in cardiovascular malformations. Lancet (Lond, Engl).
1970;1:1290–1291.
87. Heinonen OP, Slone D & Shapiro S Birth defects and drugs in pregnancy.
(Publishing Sciences Group Inc., Littleton, Massachusetts, USA, 1977).
88. Sankaran DL, Satyan. Cardiovascular effects of prenatal methamphetamine
exposure. https://clinicaltrials.gov/ct2/show/NCT04616625 (2020).
89. Dixon SD, Bejar R. Echoencephalographic findings in neonates assciiated with
maternal cocaine and methamphetamine use: Incidence and clinical correlates.
J Pediatrics. 1989;115:770–778. https://doi.org/10.1016/S0022-3476(89)80661-4
90. Maranella E, Mareri A, Nardi V, Di Natale C, Di Luca L, Conte E, et al. Severe
neurologic and hepatic toxicity in a newborn prenatally exposed to metham-
phetamine. A case report. Brain Dev. 2019;41:191–194. https://doi.org/10.1016/j.
braindev.2018.08.010
91. Chang L, Cloak C, Jiang CS, Farnham S, Tokeshi B, Buchthal S, et al. Altered
neurometabolites and motor integration in children exposed to methamphe-
tamine in utero. Neuroimage. 2009;48:391–397. https://doi.org/10.1016/j.
neuroimage.2009.06.062
92. Eze N, Smith LM, LaGasse LL, Derauf C, Newman E, Arria A, et al. School-aged
outcomes following prenatal methamphetamine exposure: 7.5-year follow-up
from the infant development, environment, and lifestyle study. J pediatrics.
2016;170:34–38.e31. https://doi.org/10.1016/j.jpeds.2015.11.070
93. Smith LM, Diaz S, LaGasse LL, Wouldes T, Derauf C, Newman E, et al. Develop-
mental and behavioral consequences of prenatal methamphetamine exposure: a
review of the Infant Development, Environment, and Lifestyle (IDEAL) study.
Neurotoxicol Teratol. 2015;51:35–44. https://doi.org/10.1016/j.ntt.2015.07.006
94. Morie KP, Crowley MJ, Mayes LC, Potenza MN. Prenatal drug exposure from
infancy through emerging adulthood: results from neuroimaging. Drug alcohol
Depend. 2019;198:39–53. https://doi.org/10.1016/j.drugalcdep.2019.01.032
95. Warton FL, Taylor PA, Warton CMR, Molteno CD, Wintermark P, Lindinger NM,
et al. Prenatal methamphetamine exposure is associated with corticostriatal
white matter changes in neonates. Metab brain Dis. 2018;33:507–522. https://
doi.org/10.1007/s11011-017-0135-9
96. Hansen RL, Struthers JM, Gospe SM Jr. Visual evoked potentials and visual
processing in stimulant drug‐exposed infants. Developmental Med Child Neurol.
1993;35:798–805.
97. LaGasse LL, Derauf C, Smith LM, Newman E, Shah R, Neal C, et al. Prenatal
methamphetamine exposure and childhood behavior problems at 3 and 5 years
of age. Pediatrics. 2012;129:681–688. https://doi.org/10.1542/peds.2011-2209
98. Derauf C, LaGasse LL, Smith LM, Newman E, Shah R, Neal CR, et al. Prenatal
methamphetamine exposure and inhibitory control among young school-age
children. J pediatrics. 2012;161:452–459.
99. Wouldes TA, LaGasse LL, Huestis MA, DellaGrotta S, Dansereau LM, Lester BM.
Prenatal methamphetamine exposure and neurodevelopmental outcomes in
children from 1 to 3 years. Neurotoxicology Teratol. 2014;42:77–84.
100. Kwiatkowski MA, Donald KA, Stein DJ, Ipser J, Thomas KG, Roos A. Cognitive
outcomes in prenatal methamphetamine exposed children aged six to seven
years. Compr psychiatry. 2018;80:24–33.
101. Kiblawi ZN, Smith LM, LaGasse LL, Derauf C, Newman E, Shah R, et al. The effect
of prenatal methamphetamine exposure on attention as assessed by con-
tinuous performance tests: results from the Infant Development, Environment,
and Lifestyle study. J Dev Behav Pediatr. 2013;34:31–37. https://doi.org/10.1097/
DBP.0b013e318277a1c5
102. Abar B, LaGasse LL, Derauf C, Newman E, Shah R, Smith LM, et al. Examining the
relationships between prenatal methamphetamine exposure, early adversity,
and child neurobehavioral disinhibition. Psychol Addict Behav.
2013;27:662–673. https://doi.org/10.1037/a0030157
103. Huang X, Chen YY, Shen Y, Cao X, Li A, Liu Q, et al. Methamphetamine abuse
impairs motor cortical plasticity and function. Mol psychiatry.
2017;22:1274–1281. https://doi.org/10.1038/mp.2017.143
104. Limanaqi F, Gambardella S, Biagioni F, Busceti CL, Fornai F. Epigenetic Effects
Induced by Methamphetamine and Methamphetamine-Dependent Oxidative
Journal of Perinatology (2022) 42:293 – 299
D. Sankaran et al.
299
Stress. Oxid Med Cell Longev. 2018;2018:4982453 https://doi.org/10.1155/2018/
4982453
105. Chang L, Smith LM, LoPresti C, Yonekura ML, Kuo J, Walot I, et al. Smaller
subcortical volumes and cognitive deficits in children with prenatal metham-
phetamine exposure. Psychiatry Res. 2004;132:95–106. https://doi.org/10.1016/j.
pscychresns.2004.06.004
106. ACOG. Methamphetamine Abuse in Women of Reproductive Age. ACOG
Committee Opinion No. 479. https://www.acog.org/Clinical-Guidance-and-
Publications/Committee-Opinions/Committee-on-Health-Care-for-Underserved-
Women/Methamphetamine-Abuse-in-Women-of-Reproductive-Age?
IsMobileSet=false, 1-5 (2011, reaffirmed 2021).
107. Wade M, Fox NA, Zeanah CH, Nelson CA. Effect of foster care intervention on
trajectories of general and specific psychopathology among children with his-
tories of institutional rearing: a randomized clinical trialeffect of foster care
intervention on psychopathology among children with histories of institutional
rearingeffect of foster care intervention on psychopathology among children
with histories of institutional rearing. JAMA Psychiatry. 2018;75:1137–1145.
https://doi.org/10.1001/jamapsychiatry.2018.2556
108. Windsor J, Benigno JP, Wing CA, Carroll PJ, Koga SF, Nelson CA 3rd, et al. Effect
of foster care on young children’s language learning. Child Dev.
2011;82:1040–1046. https://doi.org/10.1111/j.1467-8624.2011.01604.x
109. Twomey J, LaGasse L, Derauf C, Newman E, Shah R, Smith L, et al. Prenatal
methamphetamine exposure, home environment, and primary caregiver risk
factors predict child behavioral problems at 5 years. Am J Orthopsychiatry.
2013;83:64.
110. Messina N, Jeter K. Parental methamphetamine use and manufacture: child and
familial outcomes. J public child Welf. 2012;6:296–312.
111. Chu EK, Smith LM, Derauf C, Newman E, Neal CR, Arria AM, et al. Behavior problems
during early childhood in children with prenatal methamphetamine exposure.
Pediatrics. 2020;146:e20190270. https://doi.org/10.1542/peds.2019-0270
ACKNOWLEDGEMENTS
The authors would like to thank the funding sources listed below.
AUTHOR CONTRIBUTIONS
DS conceptualized, designed, wrote the first draft, reviewed, and revised the
manuscript. SL contributed to the concept, wrote part of the manuscript, provided
illustrations, reviewed, and revised the manuscript. VM contributed to the concept,
wrote part of the manuscript, reviewed, and revised the manuscript. All the authors
have approved the final version of the manuscript as submitted. All authors agree to
be accountable for all aspects of the work.
FUNDING
DS’s effort was supported by the Children’s Miracle Network research grant at
University of California Davis, Child Health Research Grant from UC Davis Pediatrics
and First Tech Federal Credit Union and Neonatal Resuscitation Program Research
Grant from Canadian Pediatric Society. SL and VM received no external funding. The
funder/sponsor did not participate in this work.
COMPETING INTERESTS
The authors declare no competing interests.
ADDITIONAL INFORMATION
Supplementary information The online version contains supplementary material
available at https://doi.org/10.1038/s41372-021-01271-8.
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Sankaran.
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