Contact Hours: 4
This educational activity is credited for 4 contact hours at completion of the activity.
Course Purpose
The purpose of this course is to provide healthcare professionals with a brief overview of the stages of fetal development, how the stages are affected by drug use, short-term health concerns, and long-term development delays in babies exposed to drugs in-utero.
Overview
Pregnancy is extremely sensitive to external elements that can cross the placental barrier, damage the uterus or placenta, or affect the mother’s health. These external elements can interfere with fetal development, affecting the maturation and calibration of organs and systems, which can lead to abnormal growth and increase the risk of short and long-term health problems. This course overviews the stages of fetal development, how the stages are affected by drug use, short-term health concerns, and long-term development delays in babies exposed to drugs in-utero.
Course Objectives
Upon completion of this course, the learner will be able to:
- Describe the stages of fetal development.
- Recognize pregnancy related complications associated with maternal drug use.
- Review the effects of teratogens on fetal development.
- Understand the signs of neonatal abstinence syndrome and options for treatment.
- Explain the long-term effects of in-utero drug exposure.
Policy Statement
This activity has been planned and implemented in accordance with the policies of FastCEForLess.com.
Disclosures
Fast CE For Less, Inc and its authors have no disclosures. There is no commercial support.
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| Blastocyst | A hollow ball of cells that forms from a fertilized egg in mammals. |
| Congenital Heart Defects | Problems with the heart’s structure that are present at birth and affect blood flow. |
| Embryo | An unborn or unhatched offspring in the process of development, in particular a human offspring during the period from approximately the second to the eighth week after fertilization. |
| Embryonic Stage | Refers to weeks 2 to week 8 of development after an egg is fertilized. |
| Euphoria | A feeling of well-being or elation. |
| Fallopian Tube | Muscular tubes that connect the ovaries and the uterus in female mammals. |
| Fetal Alcohol Syndrome | A condition in a child that results from alcohol exposure during the mother’s pregnancy. |
| Fetal Development | The process of growth and maturation of a baby in the womb. |
| Fetal Growth Restriction (FGR), also known as Intrauterine Growth Restriction (IUGR) | When the fetal weight is estimated to be below the 10th percentile for its gestational age. |
| Fetal Stage | Extends from the beginning of the ninth week after fertilization to about 38 weeks after fertilization, which is the average time of birth. |
| Fetal Withdrawal Syndrome (FWS), also known as Neonatal Abstinence Syndrome (NAS) | A collection of physiological and neurobehavioral signs of withdrawal that occur in newborns after they are repeatedly exposed to opioid drugs while in utero |
| Fetus | The unborn offspring that develops from an animal embryo. |
| Gastroschisis | A birth defect where the baby’s intestines protrude outside the abdomen. |
| Germinal Stage | The shortest stage of fetal development. It begins at conception when a sperm and egg join in your fallopian tube. |
| Gestation | The process or period of developing inside the womb between conception and birth. |
| Gestational Diabetes | A type of diabetes that can develop during pregnancy in women who don’t already have diabetes. |
| Human Immunodeficiency Virus (HIV) | A virus that attacks the body’s immune system. |
| Hypertension | High pressure in the arteries (vessels that carry blood from the heart to the rest of the body). |
| Immunological Incompetence | Inability of the immune system to function properly. |
| Intracranial Hemorrhage | Bleeding inside the skull or brain, usually caused by a head injury or a stroke. |
| Lanugo | A thin, soft, usually unpigmented hair that covers the body of a fetus or newborn. |
| Meconium Aspiration Syndrome | Occurs when a newborn breathes a mixture of meconium and amniotic fluid into the lungs around the time of delivery. |
| Miscarriage | The loss of a pregnancy before 20 weeks, affecting 10 to 20 percent of known pregnancies. |
| Necrotizing Enterocolitis | A serious gastrointestinal problem that mostly affects premature babies. The condition inflames intestinal tissue, causing it to die. |
| Neonatal Jaundice | A common condition that causes yellowing of a baby’s skin and eyes due to high bilirubin levels. |
| Neonatal Opioid Withdrawal Syndrome (NOWS) | The withdrawal symptoms that newborns experience at birth when they’ve been exposed to opioids in the womb. |
| Neural Tube | The embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. |
| Neurotoxin | Toxins that are destructive to nerve tissue (causing neurotoxicity). |
| Oligohydramnios | A disorder of amniotic fluid resulting in decreased amniotic fluid volume for gestational age |
| Perinatal Asphyxia | A lack of blood flow or gas exchange to or from the fetus in the period immediately before, during, or after the birth. |
| Philtrum | Medial cleft, is a vertical indentation in the middle area of the upper lip. |
| Placenta | A temporary organ that forms in the uterus during pregnancy. |
| Placenta Abruption | The early separation of a placenta from the lining of the uterus before completion of the second stage of labor. |
| Placental Barrier | Composed of structures that separate the maternal and the fetal blood . |
| Polyhydramnios | Excessive accumulation of amniotic fluid in the uterus during pregnancy. |
| Preeclampsia | A condition that develops in pregnant women, it is marked by high blood pressure and presence of proteins in urine. |
| Preterm Labor | When the body starts preparing for birth too early, before 37 weeks of pregnancy. |
| Respiratory Distress | A disease that affects the lungs, bronchus and respiration. |
| Sepsis | An infection of the blood stream resulting in a cluster of symptoms such as drop in a blood pressure, increase in heart rate and fever. |
| Spontaneous Abortions | The unexpected ending of a pregnancy in the first 20 weeks of gestation. |
| Stillbirth | When a baby is born dead after 24 Completed weeks of pregnancy. |
| Teratogen | An agent or factor which causes malformation of an embryo. |
| Tetrahydrocannabinol (THC) | The principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. |
| Type 2 Diabetes | A condition results from insufficient production of insulin, causing high blood sugar. |
| Umbilical Cord | A tube-like structure that connects the baby to the placenta during pregnancy. |
| Uterus | A hollow, muscular organ in the female pelvis that houses the developing baby. |
| Vernix Caseosa | The waxy white substance found coating the skin of newborn human babies. |
| Viral Hepatitis | A liver infection caused by one of five viruses: A, B, C, D, or E. |
| Zygote | A diploid cell resulting from the fusion of two haploid gametes; a fertilized ovum. |
Fetal development is an intricate and highly orderly process that occurs during gestation; the time between conception and birth.1 Typically lasting 37 – 40 weeks, gestation sees a fertilized egg grow into a fully formed human with complete organs and mature systems able to function without life support.1 This period is a critical part of every pregnancy, but it is also extremely sensitive to external elements that can cross the placental barrier, damage the uterus or placenta, or affect the mother’s health.2
These external elements can interfere with fetal development, affecting the maturation and calibration of organs and systems, leading to abnormal growth and increasing the risk of short- and long-term health problems. 2 Many common adult diseases, such as type 2 diabetes and cardiovascular conditions, have been linked to abnormal fetal growth, specifically fetal growth restriction.3
Among the most dangerous external agents are drugs, including potent prescription medications and illicit psychoactive substances such as cocaine, heroin, alcohol, and nicotine.4 Known as teratogens, these external agents can cause serious harm to a fetus altering secretory activity and restricting blood flow, resulting in severe fetal abnormalities. 4 Moreover, illicit drugs taken by the mother via unsterilized syringes also expose the fetus to transmittable diseases such as human immunodeficiency virus (HIV) and viral hepatitis, further complicating the pregnancy.5
The consequences of fetal drug exposure can be life-threatening, resulting in miscarriages, stillbirths, and neonatal deaths. Despite these known risks, approximately 5% of pregnant women use one or more addictive substances. 6 This prevalence highlights the lack of awareness and the need to continuously educate mothers and their families to avoid these preventable complications.7
This course overviews the stages of fetal development and how drug use affects it. This course also discusses the complications, short-term health concerns, and long-term development delays in babies exposed to drugs in-utero.
During pregnancy, there are three stages of fetal development, germinal, embryonic, and fetal.1
The germinal stage is the shortest phase of fetal development, beginning when an egg is fertilized by a sperm (conception) to form a zygote. This zygote travels down the fallopian tube to the uterus over the next 5 – 7 days, dividing and multiplying rapidly to eventually create two structures: the blastocystand the placenta.This blastocyst implants itself in the uterine lining, and if successful, triggers the production of hormones to support pregnancy and stop the menstrual cycle. 1
Now begins the embryonic stage. 1 The blastocyst, now called an embryo, begins to take on human characteristics such as the head, eyes, mouth, and limbs.8 Primitive structures of organs and systems also form, such as the neural tube, which later matures to become the brain and spinal cord. This period lasts from approximately week 3 to Week 7 – 8.1
The final and longest stage of development is called the fetal stage and starts from Week 9 onward until birth. The embryo is now called a fetus.9 As this stage is the longest, it is typically divided by trimester, periods of 12 weeks, counted from the final day of a woman’s last menstrual period as it is difficult to accurately determine the date of conception.2
To track fetal growth during gestation, healthcare professionals use ultrasound imaging and measure specific metrics such as head circumference, adnominal circumference, femur length, amniotic fluid levels, and heart rate.2 This information is used to estimate fetal weight and identify any abnormalities.5 Each trimester of fetal development is described below.
The First Trimester
The first trimester is the period from conception to the end of Week 12.1 As it includes the germinal and embryonic stages, it lays the foundation for the development of all critical body systems and bones. Compared to other trimesters, this stage sees the most rapid growth, including the formation of the placenta and umbilical cord. These structures supply the fetus with nutrients and oxygen to support its growth.10
By the end of this first trimester, the embryo, now considered a fetus, will measure 1 – 1.5 inches long and have all its major organs and systems, including the nervous system, brain, spinal cord, digestive system, and circulatory system, with a beating heart.1 However, it is critical to note that none of these systems are mature enough to survive independently outside the uterus, even with life support.1 Therefore, the fetus is still fully dependent on its mother.
Other developmental milestones include the growth of limb buds into fully-formed limbs, the formation of tooth buds, external genitalia, and eyelids. With this rapid development, fetal movement increases, becoming more noticeable in imaging.1,10
Given its importance in initiating normal development, the first trimester is also the most at-risk period, when the fetus is most vulnerable to damage and external influence. 1,5 According to the American College of Obstetricians and Gynecologists (ACOG), 80% of spontaneous abortions, also known as miscarriages, happen during the first trimester.11
The Second Trimester
The second trimester sees the maturation of all the systems formed in the first trimester.1 It is counted from the start of Week 13 to the end of Week 27.10 During this period, the fetus’s skin is red and wrinkly, covered by soft downy hair known as lanugo. To protect this underdeveloped skin, a white creamy substance known as vernix caseosa forms and covers its entire body. Also, fat begins to accumulate under the skin.1
In terms of system development, all organs will continue to mature, including the brain, which will have reached its most critical period. From Week 20 onwards, essential processes and reflexes such as sucking and swallowing begin. Additionally, the fetus will begin to experience cycles of wakefulness and sleep as it matures. By the end of Week 24, it has moved along far enough in its development to survive in a neonatal intensive care unit.1,10
By the end of the second trimester, the fetus will be between 13 – 16 inches long and weigh approximately 2 – 3 lbs. Appearance-wise, it will look more human, and its eyes will move to the front of its face, complete with eyelashes and eyebrows. Fingers and toes will be fully separated, with fingerprints and toe prints.1,10
The fetus will also be able to open its eyelids, turn from side to side and extend its limbs with progressively increasing intensity. By the end of this trimester, the mother should be able to feel fetal movement.1,10
A fetus born in the tail-end of the second trimester is a premature birth, and with immediate intensive care, is likely to survive. However, it may suffer from developmental delays, chronic respiratory problems, or impairments in hearing and vision. 1,10
The Third Trimester
The final phase of pregnancy is known as the third trimester.1 It starts from the beginning of Week 28 until birth by Week 37 – 40 (full-term). Throughout this stage, the fetus will grow in size and weight to be healthy enough to survive unsupported outside the uterus.1,10
By the end of the third trimester, the fetus will be 19 -21 inches long, weigh between 6 – 9 lbs., and no longer have lanugo hair. Its brain, lungs, and kidneys will be fully developed and functioning. The fetus will be able to see, hear, cry, and suck its thumb. However, fetal bones are still soft, so that the fetus can pass easily through the birth canal. 1,10
In a healthy pregnancy, the risks of complications are considerably lower. However, monitoring fetal movement and heartbeat until birth is still critical in these last weeks as there is always a possibility of preterm labor or stillbirth. Moreover, the fetus is still susceptible to external agents, which can affect its cognitive abilities and lead to delays after birth. 1,10
During every pregnancy, hormonal levels fluctuate considerably to prepare and regulate the mother’s body so it can support the development of a fetus.2 These hormonal adjustments result in numerous physiological changes at a cellular level that affect all systems, from the circulatory to the digestive. Some significant changes are listed below:2
- Elevated progesterone levels with relaxed smooth muscles allow the uterus to increase from 70g to 1100g, which results in an increased capacity of the uterus from 10mL to 5L, to 1100g.
- A 20 – 30% increase in red blood cell volume, with a 45 – 55% increase in blood plasma. This is supplemented with a 30% increase in cardiac activity and a decrease in blood pressure, allowing for an enhanced blood supply to the placenta.
- White blood cell (WBC) count increases from 6 million/mL to 16 million/mL. This heightened count increases the immune response protecting the fetus from foreign microorganisms such as bacteria and viruses. During and shortly after labor, the WBC count may go as high as 20 million/mL.
- An increase in blood oxygen and a decrease in blood carbon dioxide (from 40 mm Hg to 30 mm Hg by Week 20), which creates a greater gradient that enhances oxygen delivery to the fetus.
Due to these changes, many pregnant women experience an array of symptoms that include but are not limited to high (or low) blood pressure, skin conditions, indigestion, acidity, constipation, nausea, morning sickness, and fatigue.2
Substances such as drugs and alcohol can exacerbate any of these conditions, as it interferes with the natural processes and may also upset the new hormonal balance. Depending on the potency of the substance and frequency of use, drugs can also cause serious physiological, emotional, and behavioral concerns that can further complicate the pregnancy. The most common complications include hypertension, gestational diabetes, infection, preterm labor, miscarriage, and stillbirth.4,5,6,7
Hypertension
Also known as high blood pressure, drugs with vasoconstrictive effects increase arterial pressure, reducing the amount of blood moving through the blood vessels to vital organs such as the placenta and uterus.4,5 Not only does high blood pressure increase the risks of damage to organs, it also increases the risk of preterm labor, miscarriage, stillbirth, and other serious conditions such as preeclampsia.4,5,6,12
Preeclampsia is a severe hypertension complication, and if left untreated, can be life-threatening for both the mother and fetus. Even with treatment, it can still damage a pregnant woman’s kidneys, liver, and cardiovascular function resulting in long-term health problems.12
Gestational Diabetes
Gestational diabetes causes blood sugar levels to rise and fall unregulated, affecting multiple systemic processes and increasing blood pressure.13 Drug use during pregnancy may interfere with insulin production, prompting the onset of gestational diabetes. If left untreated, it can increase the risk of preeclampsia, polyhydramnios (excessive amniotic fluid), preterm labor, and fetal loss.4,5,6
Infection
Illicit drug use via unsterilized syringes during pregnancy may introduce harmful viruses and bacteria to the body, which can cross the placental barrier to reach the fetus. Moreover, drug use can weaken a pregnant woman’s immune system, making her and the fetus more susceptible to infection. This exposure can contribute to miscarriage, preterm labor, stillbirths, and congenital disabilities such as deafness, blindness, and deformities. 4,5,6
Preterm Labor, Miscarriage, and Stillbirth
Given the numerous side effects of drugs, their usage during pregnancy can induce preterm labor (birth before Week 37).1,11 A fetus born during this time is still immature, with underdeveloped systems, and will require immediate medical attention to increase its chances of survival. However, if preterm labor is triggered too early, it can result in neonatal death regardless of medical interventions.1,11
Drug use also increases the likelihood of miscarriage (fetal loss before Week 20) and stillbirth (fetal loss after Week 20).1 While the exact mechanism of this loss is unclear, it is understood that drugs can alter hormonal levels, destabilizing a pregnant mother’s body. 4,5,6
Also, drugs restrict blood flow, decreasing the amount of nutrients and oxygen that reaches the fetus. This interference disrupts fetal developmental processes, damaging organs. These adverse effects make it difficult to support the pregnancy, thus resulting in a miscarriage or stillbirth. 4,5,6
The long-term effects of in-utero drug exposure depend on several factors, including the type of drug, the amount used, the frequency of use, and its timing in terms of trimester. Moreover, how a substance reacts with a fetus varies from case to case, making it increasingly challenging to predict potential developmental issues and delays.38
What is known, is that infants who survive the immediate complications following their birth have some degree of damage to their brain and other organ systems because of in-utero drug exposure.5,6,7 Additionally, infants may also suffer from the adverse effects of any medical therapies or interventions that were necessary following their birth to keep them alive. Combined, these factors increase the risk of developmental delays and poor physical growth.38
Case studies have shown that learning disabilities and behavioral problems become apparent as these infants grow into children and may continue through to adulthood. These disabilities include disrupted visual perception, impaired cognitive performance and information processing, problems with language and memory, difficulties with problem-solving, difficulties with self-regulation, limited sustained attention to tasks, lower intelligence and academic underachievement and hyperactivity and emotional disbalances.38
One of the most challenging aspects of preventing drug use during pregnancy is stopping usage in time. Most women are unaware of their pregnancy, and it isn’t until they are 2 – 3 weeks late for their expected period that they find out.1,2,10 By this time, their pregnancy may be in or have completed its first trimester, and potential damage may have already been inflicted on the fetus.5
Therefore, awareness is the key to preventing in-utero drug exposure. Women engaging in unprotected sexual intercourse must understand the risks of drug use, illicit and prescription, so they can take measures to stop taking the drugs before becoming pregnant.5,39
For pregnant mothers using drugs, early treatment is vital. Prescription medications must be changed to safer alternatives, and rehabilitation treatment should begin as soon as possible for those with addictions.39
Treatment for drug addiction can also include prescribing detoxification and maintenance therapy, such as methadone or phenobarbital to prevent relapse.40 in addition, a comprehensive dietary plan, complete with supplements, must be provided to ensure the pregnant mother consumes the essential nutrients necessary to promote healthy fetal development.40
Throughout the pregnancy, fetal growth must be monitored closely with frequent ultrasounds. Also, drug exposure should be assessed via umbilical cord tissue and meconium samples. Prompt care can significantly reduce fetal exposure to drugs and reduces the likelihood of serious complications for both mother and fetus.5,6,7
In case any abnormalities are detected, the pregnant mother must be informed. Therapy is often required to process this situation and determine the next steps. It is important to honestly discuss the immediate treatment needed to support the unborn child through pregnancy and after birth, along with possible long-term health issues.5,40
In the case of a miscarriage or stillbirth, the healthcare professional should provide immediate medical treatment to evacuate the uterus and include aftercare therapy to help women recover from their loss.11
Fetal development is a complex process dependent on a safe environment to ensure healthy growth.1 Drug use during pregnancy can severely impair this development, drastically increasing the risk of life-threatening complications for both the mother and the fetus. These complications can result in preterm labor, premature birth, miscarriage, and stillbirths.5
In-utero drug exposure can damage vital fetal organs and systems, leading to abnormalities such as fetal growth restriction, which in turn can result in birth defects, disabilities, and other health issues.14Infants born may also suffer from a myriad of health complications after birth, such as fetal withdrawal syndrome.22
Babies who survive short-term medical challenges of drug exposure are often plagued with developmental delays, cognitive disabilities, and behavior problems, affecting their long-term quality of life.38
In-utero drug exposure defects and disabilities are among the most preventable birthing issues in the country. Women who have reached childbearing age must be aware of and understand the dangers of drug use during pregnancy. Those on potent prescription medications should seek alternatives before becoming pregnant, and those dealing with addictions must seek treatment.40
However, it is important to recognize the challenges of avoiding fetal drug exposure in time. Early screening and treatment are necessary to ensure drugs are eliminated from a pregnant mother’s system and she does not relapse during pregnancy.39 Fetal development in such cases must be closely monitored and assessed to evaluate fetal growth and identify any abnormalities. Regardless of the findings and diagnosis, pregnant mothers should be supported medically and emotionally throughout the process so they are capable of making informed decisions regarding their pregnancy.11,40
- Cleveland Clinic. (2020, April 16). Stages Of Pregnancy & Fetal Development | Cleveland Clinic. Cleveland Clinic. https://my.clevelandclinic.org/health/articles/7247-fetal-development-stages-of-growth
- Talbot, L., & Maclennan, K. (2016). Physiology of pregnancy. Anaesthesia & Intensive Care Medicine, 17(7), 341-345. https://doi.org/10.1016/j.mpaic.2016.04.010/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2878887/
- Genetic Alliance. (2010, February 17). Teratogens/Prenatal Substance Abuse. Nih.gov; Genetic Alliance. https://www.ncbi.nlm.nih.gov/books/NBK132140/
- Ross, E. J., Graham, D. L., Money, K. M., & Stanwood, G. D. (2015). Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn. Neuropsychopharmacology, 40(1), 61–87. https://doi.org/10.1038/npp.2014.147
- WENDELL, A. D. (2013). Overview and Epidemiology of Substance Abuse in Pregnancy. Clinical Obstetrics and Gynecology, 56(1), 91–96. https://doi.org/10.1097/GRF.0b013e31827feeb9
- Sachdeva, P., Patel, B., & Patel, B. (2009). Drug use in pregnancy; a point to ponder! Indian Journal of Pharmaceutical Sciences, 71(1), 1. https://doi.org/10.4103/0250-474x.51941
- National Cancer Institute. (2011, February 2). https://www.cancer.gov/publications/dictionaries/cancer-terms/def/embryo. www.cancer.gov. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/embryo
- https://www.cancer.gov/publications/dictionaries/cancer-terms/def/fetus. (2011, February 2). www.cancer.gov. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/fetus.
- Rossavik, I. K., Brandenburg, M. A., & Venkataraman, P. S. (1992). Understanding the different phases of fetal growth. Hormone Research, 38(5-6), 203–207. https://doi.org/10.1159/000182543
- Early Pregnancy Loss. (2018). Acog.org. https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/11/early-pregnancy-loss
- Leeman, L., & Fontaine, P. (2008). Hypertensive disorders of pregnancy. American Family Physician, 78(1), 93–100. https://pubmed.ncbi.nlm.nih.gov/18649616/
- Gandhi, R., & Marlow, N. (2018). Fetal growth restriction and neonatal outcomes. Placental-Fetal Growth Restriction, 237-245. https://doi.org/10.1017/9781316181898.028
- GUNATILAKE.RAVINDU. (2018). Drug Use During Pregnancy. MSD Manual Consumer Version; MSD Manuals. https://www.msdmanuals.com/home/women-s-health-issues/drug-use-during-pregnancy/drug-use-during-pregnancy
- Larkby, C., & Day, N. (1997). The Effects of Prenatal Alcohol Exposure. Alcohol Health and Research World, 21(3), 192–198. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826810/
- CAIN, M. A., BORNICK, P., & WHITEMAN, V. (2013). The Maternal, Fetal, and Neonatal Effects of Cocaine Exposure in Pregnancy. Clinical Obstetrics and Gynecology, 56(1), 124–132. https://doi.org/10.1097/grf.0b013e31827ae167
- Roncero, C., Valriberas-Herrero, I., Mezzatesta-Gava, M., Villegas, J. L., Aguilar, L., & Grau-López, L. (2020). Cannabis use during pregnancy and its relationship with fetal developmental outcomes and psychiatric disorders. A systematic review. Reproductive Health, 17(1). https://doi.org/10.1186/s12978-020-0880-9
- Wilson, K. M., Torok, M. R., Wei, B., Wang, L., Robinson, M., Sosnoff, C. S., & Blount, B. C. (2017). Detecting biomarkers of secondhand marijuana smoke in young children. Pediatric Research, 81(4), 589–592. https://doi.org/10.1038/pr.2016.261
- CDC. (2021, September 24). Heroin | CDC’s Response to the Opioid Overdose Epidemic | CDC. Www.cdc.gov. https://www.cdc.gov/opioids/basics/heroin.html
- Yazdy, M. M., Desai, R. J., & Brogly, S. B. (2015). Prescription Opioids in Pregnancy and Birth Outcomes: A Review of the Literature. Journal of Pediatric Genetics, 4(2), 56–70. https://doi.org/10.1055/s-0035-1556740
- Bagwell, G. A. (2019). Neonatal abstinence syndrome. Comprehensive Neonatal Nursing Care. https://doi.org/10.1891/9780826139146.0030https://www.ncbi.nlm.nih.gov/books/NBK551498/
- Concerns with ketamine and esketamine. (2021). Ketamine, 121-140. https://doi.org/10.7551/mitpress/13258.003.0008
- Mandal, S., Sinha, V., & Goyal, N. (2019). Efficacy of ketamine therapy in the treatment of depression. Indian Journal of Psychiatry, 61(5), 480. https://doi.org/10.4103/psychiatry.indianjpsychiatry_484_18
- Capitanio, J. P., Del Rosso, L. A., Calonder, L. A., Blozis, S. A., & Penedo, M. C. T. (2012). Behavioral effects of prenatal ketamine exposure in rhesus macaques are dependent on MAOA genotype. Experimental and Clinical Psychopharmacology, 20(3), 173–180. https://doi.org/10.1037/a0026773
- Bais, B., Molenaar, N. M., Bijma, H. H., Hoogendijk, W. J., Mulder, C. L., Luik, A. I., Lambregtse-van den Berg, M. P., & Kamperman, A. M. (2020). Prevalence of benzodiazepines and benzodiazepine-related drugs exposure before, during and after pregnancy: A systematic review and meta-analysis. Journal of Affective Disorders, 269, 18-27. https://doi.org/10.1016/j.jad.2020.03.014
- Ativan ® C-IV (lorazepam) Tablets Rx only https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/017794s044lbl.pdf
- Wong, S. H., & Chan, F. K. (2016). Adverse effects of NSAIDs in the gastrointestinal tract: Risk factors of gastrointestinal toxicity with NSAIDs. NSAIDs and Aspirin, 45-59. https://doi.org/10.1007/978-3-319-33889-7_4
- Ibuprofen. (1994). PubMed; Organization of Teratology Information Specialists (OTIS). https://www.ncbi.nlm.nih.gov/books/NBK582759/
- Kumud, M. (2018). Maternal & Fetal outcome after diagnosis of Oligohydramnios at term. Journal of Medical Science And clinical Research, 6(3). https://doi.org/10.18535/jmscr/v6i3.92
- Low-Dose Aspirin Use During Pregnancy. (n.d.). Www.acog.org. https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2018/07/low-dose-aspirin-use-during-pregnancy
- Van Doorn, R., Mukhtarova, N., Flyke, I. P., Lasarev, M., Kim, K., Hennekens, C. H., & Hoppe, K. K. (2021). Dose of aspirin to prevent preterm preeclampsia in women with moderate or high-risk factors: A systematic review and meta-analysis. PLOS ONE, 16(3), e0247782. https://doi.org/10.1371/journal.pone.0247782
- Neonatal withdrawal – an overview | ScienceDirect Topics. (n.d.). www.sciencedirect.com. https://www.sciencedirect.com/topics/medicine-and-dentistry/neonatal-withdrawal
- McQueen, K., & Murphy-Oikonen, J. (2016). Neonatal abstinence syndrome. New England Journal of Medicine, 375(25), 2468-2479. https://doi.org/10.1056/nejmra1600879 https://www.ncbi.nlm.nih.gov/books/NBK551498/
- [Leyenaar, J. K., Schaefer, A. P., Wasserman, J. R., Moen, E. L., O’Malley, A. J., & Goodman, D. C. (2021). Infant Mortality Associated With Prenatal Opioid Exposure. JAMA Pediatrics. https://doi.org/10.1001/jamapediatrics.2020.6364
- Lund, I. O., Fischer, G., Welle-Strand, G. K., O’grady, K. E., Debelak, K., Morrone, W. R., & Jones, H. E. (2013). A Comparison of Buprenorphine + Naloxone to Buprenorphine and Methadone in the Treatment of Opioid Dependence during Pregnancy: Maternal and Neonatal Outcomes. Substance Abuse: Research and Treatment, 7, SART.S10955. https://doi.org/10.4137/sart.s10955
- Kraft, W. K., Adeniyi-Jones, S. C., Chervoneva, I., Greenspan, J. S., Abatemarco, D., Kaltenbach, K., & Ehrlich, M. E. (2017). Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome. New England Journal of Medicine, 376(24), 2341–2348. https://doi.org/10.1056/nejmoa1614835
- Behnke, M., & Smith, V. C. (2013). Prenatal Substance Abuse: Short- and Long-term Effects on the Exposed Fetus. PEDIATRICS, 131(3), e1009–e1024. https://doi.org/10.1542/peds.2012-3931
- Price, H. R., Collier, A. C., & Wright, T. E. (2018). Screening Pregnant Women and Their Neonates for Illicit Drug Use: Consideration of the Integrated Technical, Medical, Ethical, Legal, and Social Issues. Frontiers in Pharmacology, 9(961). https://doi.org/10.3389/fphar.2018.00961
- Abuse, N. I. on D. (2021, December). What treatment is available for pregnant mothers and their babies? National Institute on Drug Abuse.
- https://nida.nih.gov/publications/research-reports/medications-to-treat-opioid-addiction/what-treatment-available-pregnant-mothers-their-babies
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