Tag: pregnancy

Categories : HIV Obstetrics & GynaecologyTags :

Dolutegravir-based ART is Better for Pregnant Individuals with HIV-1

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Dolutegravir-based antiretroviral therapies (ART) for HIV-1 are more effective for pregnant individuals than some other ART regimens commonly used in the US and Europe, according to a study available online in NEJM.

The study, led by Harvard T.H. Chan School of Public Health researchers, showed that pregnant individuals who took dolutegravir-based regimens had a high probability of being virally suppressed at delivery. No differences were seen in adverse birth outcome risks (preterm birth, low birth weight, small for gestational age, or neonatal death) between dolutegravir-based regimens and the other contemporary regimens.

“Globally, a dolutegravir-based regimen is currently recommended for treating HIV, and this is the first study to directly compare regimens including dolutegravir to other antiretroviral regimens, such as raltegravir-based regimens, that are also listed as ‘Preferred’ in US perinatal guidelines,” said senior research scientistKunjal Patel, lead author of the study.

Dolutegravir, is a newer antiretroviral part of a once-a-day regimen that has been shown to be more effective, easier to tolerate, and less likely to create new drug resistance in people with HIV-1. However, limited data have been available about its effectiveness and safety in pregnancy compared with regimens that commonly have been used during pregnancy in the US and Europe.

In the current observational study, the researchers compared dolutegravir use in pregnancy with atazanavir/ritonavir, darunavir/ritonavir, and raltegravir antiviral regimens that are currently classified as “Preferred” for use in pregnancy in the US About half of the participants started ART before conception. At delivery, 96.7% of pregnancies of participants who received dolutegravir were virally suppressed, whereas those of participants who took atazanavir/ritonavir or raltegravir had viral suppression of 84.0% and 89.2%, respectively.

“We think the observed differences are due to dolutegravir’s ability to rapidly decrease viral loads and its ease of use as part of a once-daily regimen that’s available as a fixed-dose combination,” said Patel. “Our results highlight the continual need for systematic studies that compare new antiretroviral regimens with those already in clinical practice to help inform the evolution of guidelines and clinical practice over time.”

Source: Harvard T.H. Chan School of Public Health

Categories : Environmental Effects Obstetrics & GynaecologyTags :

Maternal Phthalates Exposure Increases Preterm Birth Risk

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pregnant woman holding her belly
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A National Institutes of Health study has found that pregnant women who were exposed to multiple phthalates during pregnancy had an increased risk of preterm birth. The most significant correlation was for a phthalate most commonly used in nail polish and cosmetics.

Used in a great variety of products such as cosmetics and food packaging, phthalates are endocrine-disrupting chemicals that are known to have a wide range of health effects on humans. This especially true of children, due to their impact on the developmental system, as well as the reproductive system.

Researchers analysed data from more than 6000 pregnant women in the US, and found that women with higher concentrations of several phthalate metabolites in their urine had increased risks of preterm birth.

“Having a preterm birth can be dangerous for both baby and mom, so it is important to identify risk factors that could prevent it,” said epidemiologist Kelly Ferguson, PhD, the senior author on the study published in JAMA Pediatrics.

Data from 16 US studies that included individual participant data on prenatal urinary phthalate metabolites (representing exposure to phthalates) as well as the timing of delivery. Researchers analysed data from a total of 6045 pregnant women who delivered between 1983-2018, 9% of whom delivered preterm. Phthalate metabolites were detected in more than 96% of urine samples.

Exposure to four of the 11 phthalates found in the pregnant women was associated with a 14–16% greater probability of having a preterm birth. The most consistent findings were for exposure to a phthalate that is used commonly in personal care products like nail polish and cosmetics.

Using statistical models to simulate interventions that reduce phthalate exposures, the researchers found that reducing the mixture of phthalate metabolite levels by 50% could prevent preterm births by 12% on average. Interventions targeting behaviours, such as trying to select phthalate-free personal care products (if listed on label), voluntary actions from companies to reduce phthalates in their products, or changes in standards and regulations could contribute to exposure reduction and protect pregnancies.

“It is difficult for people to completely eliminate exposure to these chemicals in everyday life, but our results show that even small reductions within a large population could have positive impacts on both mothers and their children,” said Barrett Welch, PhD, first author on the study.

Eating fresh, home-cooked food, avoiding processed food that comes in plastic containers or wrapping, and selecting fragrance-free products or those labeled ‘phthalate-free’, are examples of things people can do that may reduce their exposures. Changes to the amount and types of products that contain phthalates could also reduce exposures.

The researchers are undertaking further studies to better understand the mechanisms behind how phthalates affect pregnancy and to find ways for mothers to reduce their exposures.

Source: National Institutes of Health

Categories : COVID Obstetrics & GynaecologyTags :

Nitrous Oxide Safe and Effective Therapy for Severe COVID in Pregnancy

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High dose inhaled nitric oxide gas (iNO) is a safe and effective respiratory therapy for pregnant women hospitalised with severe COVID pneumonia, resulting in faster weaning from oxygen and shorter hospital stay, according to a study published in Obstetrics & Gynecology. Massachusetts General Hospital (MGH) researchers reported that the addition of twice-daily nitric oxide to standard of care oxygen therapy decreased the respiratory rate of pregnant women with low oxygenation levels of the blood without causing any side effects.

“To date, very few respiratory treatments to complement supplemental oxygenation in COVID pregnant patients have been tested,” explained the study’s senior author, Lorenzo Berra, MD. “Investigators from all four medical centers that participated in our study agreed that administration of high dose nitric oxide through a snug-fitting mask has enormous potential as a new therapeutic strategy for pregnant patients with COVID.”

Pneumonia triggered by COVID is particularly threatening to pregnant women since it may quickly progress to hypoxaemia, requiring hospitalisation and cardiopulmonary support. “Compared to non-pregnant female patients with COVID, pregnant women are three times more likely to need intensive care unit admission, mechanical ventilation, or advanced life support, and four times more likely to die,” noted lead author Carlo Valsecchi, MD. “They also face a greater risk of obstetric complications such as preeclampsia, preterm delivery, and stillbirth.”

Nitric oxide is a therapeutic gas that was initially approved by the U.S. Food and Drug Administration in 1999 for inhalation treatment of intubated and mechanically ventilated newborns with hypoxic respiratory failure. With MGH driving many early studies, iNO in high concentrations was also shown to be effective as an antimicrobial in reducing viral replication of SARS-CoV-1 and, more recently, SARS CoV-2. During the first wave of COVID, MGH treated six non-intubated pregnant patients with iNO at high doses of up to 200 parts per million (ppm). Favourable outcomes with iNO led MGH clinicians to offer this treatment to other pregnant patients, and motivated the present study.

Researchers and clinicians from multiple departments in four hospitals – including critical care medicine, respiratory care, and maternal foetal medicine – studied 71 pregnant patients with severe COVID pneumonia admitted to these hospitals, 20 of whom received iNO200 twice daily. The study found that iNO therapy at this dosage, when compared to standard of care alone, resulted in reductions in the need for supplemental oxygen and in hospital and ICU lengths of stay. No adverse events related to the intervention were reported in either mothers or their babies.

“Being able to wean patients from respiratory support quicker could have other profound implications, including reducing stress on women and their families, lowering the risk of hospital-acquired infections, and relieving the burden on the health care system,” noted Dr Berra. “Above all, our study supports the safety of high dose nitric oxide in the pregnant population, and we hope more physicians will consider incorporating it into carefully monitored treatment regimens.”

Source: Massachusetts General Hospital

Categories : UncategorizedTags :

Secrets of Pregnant Mothers’ ‘Super Antibodies’ Revealed

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Pregnant mothers have the ability to confer greater immunity to the vulnerable developing foetus with ‘super antibodies’. Now, a far-reaching study published in Nature provides a surprising explanation of how this actually works, and what it could mean for preventing death and disability from a wide range of infectious diseases.

The findings suggest the amped-up antibodies that expecting mothers produce could be mimicked to create new drugs to treat diseases as well as improved vaccines to prevent them.

“For many years, scientists believed that antibodies cannot get inside cells. They don’t have the necessary machinery. And so, infections caused by pathogens that live exclusively inside cells were thought to be invisible to antibody-based therapies,” said Sing Sing Way, MD. “Our findings show that pregnancy changes the structure of certain sugars attached to the antibodies, which allows them to protect babies from infection by a much wider range of pathogens.”

“The maternal-infant dyad is so special. It’s the intimate connection between a mother and her baby,” says John Erickson, MD, PhD, first-author of the study.

Drs Way and Erickson are both part of Cincinnati Children’s Center for Inflammation and Tolerance and the Perinatal Institute, which strives to improve outcomes for all pregnant women and their newborns.

Erickson continues, “This special connection starts when babies are in the womb and continues after birth. I love seeing the closeness between mothers and their babies in our newborn care units. This discovery paves the way for pioneering new therapies that can specifically target infections in pregnant mothers and newborns babies. I believe these findings also will have far-reaching implications for antibody-based therapies in other fields.”

How mothers make super antibodies
The new study identifies the specific change in the sugar. During pregnancy, the “acetylated” form of sialic acid (one of the sugars attached to antibodies) shifts to the “deacetylated” form. This subtle molecular shift lets immunoglobulin G (IgG) take on an expanded protective role by stimulating immunity through receptors that respond specifically to deacetylated sugars.

“This change is the light switch that allows maternal antibodies to protect babies against infection inside cells,” Dr Way said.

“Mothers always seem to know best,” Dr Erickson added.

Revved-up antibodies can be produced in the lab
The research team pinned down the key biochemical differences between antibodies in virgin mice compared to pregnant ones. They also identified the enzyme naturally expressed during pregnancy responsible for driving this transformation.

Further, the team successfully restored lost immune protection by supplying lab-grown supplies of the antibodies from healthy pregnant mice to pups born to mothers that were gene-edited to lack the ability to remove acetylation from antibodies to enhance protection.

Hundreds of monoclonal antibodies have been produced as potential treatments for various disorders, including COVID, with a variety of results.

Dr Way said this molecular alteration can be replicated to change how antibodies stimulate the immune system to fine-tune their effects. This potentially could lead to improved treatments for infections caused by other intracellular pathogens including HIV and respiratory syncytial virus (RSV), a common virus that poses serious risks to infants.

Another reason to accelerate vaccine development
“We’ve known for years the many far-reaching benefits of breastfeeding,” Dr Erickson said. “One major factor is the transfer of antibodies in breastmilk.”

The study shows that nursing mothers retain the molecular switch, passing through the antibodies to their newborns.

Additionally, Dr Way says the findings underscore the importance of receiving all available vaccines for women of reproductive age – as well as the need for researchers to develop even more vaccines against infections that which are especially prominent in women during pregnancy or in newborn babies.

“The immunity needs to exist within the mother for it to be transferred to her child,” Dr Way said. “Without natural exposures or immunity primed by vaccination, when that light switch flips during pregnancy, there’s no electricity behind it.”

Source: Cincinnati Children’s Hospital Medical Center

Categories : Obstetrics & GynaecologyTags :

Study Confirms Analgesics during Pregnancy Carries Risks for Newborns

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Pregnant with ultrasound image
Source: Pixabay

Researchers have called for a reassessment of medical advice on analgesic use during pregnancy after a new study published in BMJ Open found that pregnant women using over-the-counter analgesics are about 1.5 times more likely to have a baby with health issues.

The study found elevated risks for preterm delivery, stillbirth or neonatal death, physical defects and other problems compared with the offspring of mothers who did not take such medications.

Between 30% and 80% of women globally use non-prescription analgesics in pregnancy for pain relief. However, there is presently great variation in evidence for safety of use during pregnancy, with some drugs considered safe and others not.

“We would encourage a strong reinforcement of the official advice for pregnant women.”

Aikaterini Zafeiri, first author of the study

The study analysed data from more than 151 000 pregnancies over 30 years (1985–2015) which contained medical notes for non-prescribed maternal consumption of five common analgesic. These were paracetamol, aspirin, and non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac, naproxen and ibuprofen – either as single compounds or in combinations.

Overall, 29% of women have taken over-the-counter analgesics during pregnancy, a figure which more than doubled to 60% during the last seven years of the 30-year study period.

When asked specifically at their first antenatal clinic visit, as opposed to later in pregnancy or after labour, 84% of women using painkillers reported use during the first 12 weeks after conception. However, the duration and dose of use and medical reason for use were not recorded.

Nevertheless, given that up to 60% of women reported using over the counter analgesics, they could not all have underlying medical conditions that would cause the increased risks seen in this study.

The study found increases in the following:

  • Neural tube defects: 64% more likely.
  • Admission to a neonatal unit: 57% more likely.
  • Neonatal death: 56% more likely.
  • Premature delivery before 37 weeks: 50% more likely.
  • Baby’s condition at birth based on APGAR score of less than 7 at five minutes: 48% more likely.
  • Stillbirth: 33% more likely.
  • Birthweight under 2.5 kg: 28% more likely.
  • Hypospadias, a birth defect affecting the penis: 27% more likely.

First author of the paper, Aikaterini Zafeiri of the University of Aberdeen said: “In light of the study findings, the ease of access to non-prescription painkillers, in combination with availability of mis-information as well as correct information through the internet, raises safety concerns.

“This is especially when mis-informed or partially-informed self-medication decisions are taken during pregnancy without medical advice.

“It should be reinforced that paracetamol in combination with NSAIDs is associated with a higher risk and pregnant women should always consult their doctor or midwife before taking any over-the-counter drugs. We would encourage a strong reinforcement of the official advice for pregnant women.”

Source: University of Aberdeen

Categories : Obstetrics & GynaecologyTags :

No Added Seizure Risk from Antidepressant Use in Pregnancy

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Pregnant with ultrasound image
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A large Swedish study in the journal Neurology found that pregnant women taking selective serotonin reuptake inhibitors (SSRIs) or selective norepinephrine reuptake inhibitors (SNRIs) during the first trimester of was not linked to an increased risk for neonatal seizures and epilepsy in childhood.

Any increase in seizures or epilepsy is likely due to other factors, the researchers said.

“It’s not likely the medications themselves that are causing the seizures and epilepsy in children, but rather the reasons why these women are taking the medication,” according to Kelsey Kathleen Wiggs, a PhD candidate at Indiana University in Bloomington. There are also the other background factors that differ between women who do and do not use SSRI/SNRIs.

“When it rains, it pours,” Wiggs said. “Women who are taking antidepressants in pregnancy are doing that for lots of different reasons, and they might be at risk for different things than women who aren’t taking those medications in pregnancy.”

The study found an elevated risk for neonatal seizures (risk ratio [RR] 1.41) and epilepsy in early childhood (HR 1.21) among offspring of mothers who used antidepressants in pregnancy.

Adjustment for maternal indications for SSRI/SNRI use and background factors like smoking during pregnancy revealed that they were drivers for both associations: neonatal seizures (RR 1.10); epilepsy diagnosis at 5 years (HR 0.96). Parental history of epilepsy was not found to affect the association.

The findings provide a “conclusive answer” to these concerns with using SSRI/SNRIs during pregnancy, according to Anne Berg, PhD, and Torin Glass, BM, Bch, BAO.

“[SSRI/SNRIs] have been demonstrated to have serotonergic central nervous system effects and are associated with an observable withdrawal syndrome which may be seen in the neonate following in utero exposure,” noted Drs Berg and Glass, in an accompanying editorial.

“The authors understood that with a population-based data registry and huge sample size, they had more than sufficient statistical power to detect even a modest increase in risk,” the editorialists wrote. “They tested this hypothesis and were able to reject it, definitively!”

In order to determine whether antidepressants had a causal association with infant seizures and childhood epilepsy, the researchers analysed data from national Swedish healthcare registries on a total of 1 721 274 children in Sweden born between 1996 and 2011.

Participants were divided into two groups: one group of mothers who reported use of an SSRI (fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine, escitalopram) or SNRI (venlafaxine, duloxetine) during the first trimester of pregnancy (n = 24 308), and another group with no reported antidepressant use (n = 1 696 966).

Source: MedPage Today

Categories : Neurology Obstetrics & GynaecologyTags :

Scientists Discover the Neurological Basis of Food Cravings in Pregnancy

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By examining mice, which get pregnancy cravings similar to humans, scientists have identified the neurological basis of food craving during pregnancy.

During pregnancy, the mother’s body undergoes a series of physiological and behavioural changes to create an environment facilitating the embryo’s development. Frequent consumption of tasty, high calorie foods driven by the cravings contributes to weight gain and obesity in pregnancy, with possible negative consequences for the baby’s health.

“There are many myths and popular beliefs regarding these cravings, although the neuronal mechanisms that cause them are not widely known,” noted study leader March Claret, at the University of Barcelona and leader of the study published in the journal Nature Metabolism.

The researchers found that the brains of pregnant female mice undergoes changes in the functional connections of the brain reward circuits, as well as the taste and sensorimotor centres. Mice, like pregnant women, are also more sensitive to sweet food, and develop binge-eating behaviours towards high calorie foods. “The alteration of these structures made us explore the mesolimbic pathway, one of the signal transmission pathways of dopaminergic neurons. Dopamine is a key neurotransmitter in motivational behaviours,” notes Claret, member of the Department of Medicine of the UB and the Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM).

The team saw that dopamine levels and dopamine receptor (D2R) activity increased in the nucleus accumbens, a brain region involved in the reward circuit. “This finding suggests that the pregnancy induces a full reorganisation of the mesolimbic neural circuits through the D2R neurons,” noted study leader Roberta Haddad-Tóvolli. “These neuronal cells – and their alteration – would be responsible for the cravings, since food anxiety, typical during pregnancy, disappeared after blocking their activity.”

The team demonstrated that persistent cravings have consequences for the offspring, affecting the metabolism and development of neural circuits that regulate food intake, leading to weight gain, anxiety and eating disorders. “These results are shocking, since many of the studies are focused on the analysis of how the mother’s permanent habits – such as obesity, malnutrition, or chronic stress – affect the health of the baby. However, this study indicates that short but recurrent behaviours, such as cravings, are enough to increase the psychological and metabolic vulnerability of the offspring,” concluded Claret.

The conclusions of the study could contribute to the improvement of nutritional guidelines for pregnant women in order to ensure a proper prenatal nutrition and prevent the development of diseases.

Source: University of Barcelona

Categories : COVID Obstetrics & GynaecologyTags :

Severe COVID Raises Risk of Pregnancy Complications

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A University of Oxford study of over 4000 pregnant women indicates that severe COVID in pregnancy increases the risk of pre-labour caesarean birth, a very or extreme preterm birth, stillborn birth, and the need for admission to a neonatal unit.  

The study, published in Acta Obstetricia et Gynecologica Scandinavica, included 4436 pregnant women hospitalised in the UK with symptomatic COVID from March 1, 2020 to October 31, 2021, of whom 13.9% of had severe COVID. As well as having increased risks of adverse pregnancy-related outcomes, women with severe infection were more likely to be aged 30 years or over, be overweight or obese, be of mixed ethnicity, or have gestational diabetes compared with those with mild or moderate infection.  

“This new analysis shows that certain pregnant women admitted to a hospital with COVID face an elevated risk of severe disease. However, it shows once again the strongly protective effect of vaccination against severe disease and adverse outcomes for both mother and baby,” said senior author Marian Knight, FMedSci, of the University of Oxford. “This study emphasises the importance of ensuring that interventions to promote vaccine uptake are particularly focused towards those at highest risk.”

Source: Wiley

Categories : Obstetrics & GynaecologyTags :

Endocrine-disrupting Chemicals Present in Many Pregnancies

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Researchers in Europe have shown that up to 54% of pregnant women in Sweden were exposed to complex mixtures of endocrine-disrupting chemicals disruptive to brain development.

While current risk assessment tackles chemicals and their allowable exposures on an individual basis, these findings show the need to take mixtures into account for future risk assessment approaches. The study was published in Science.

A growing body of evidence has shown that industrially produced chemicals have endocrine disrupting properties and can thus be dangerous to human and animal health and development. A huge number of new compounds is released every year into the environment during the production of plastic derivatives and other goods.

While exposures for individual chemicals falls below thresholds, exposure to the same chemicals in complex mixtures can still impact human health. However, all current exposure thresholds, are based on chemicals being examined individually. Therefore, an alternative strategy needed to be tested, in which the actual mixtures measured in real life exposures could be tested as such in both the epidemiological and experimental setting. The EDC-MixRisk project set out to tackle this unmet need.

“The uniqueness of this comprehensive project is that we have linked population data with experimental studies, and then used this information to develop new methods for risk assessment of chemical mixtures,” said Carl-Gustaf Bornehag, professor at Karlstad University, Project Manager of the SELMA study.

The study was conducted in three steps:

  1. A mixture of chemicals in the blood and urine of pregnant women was identified in the Swedish pregnancy cohort SELMA, associated with delayed language development in children at 30 months. This critical mixture included a number of phthalates, bisphenol A, and perfluorinated chemicals.
  2. Experimental studies uncovered the molecular targets through which human-relevant levels of this mixture disrupted the regulation of endocrine circuits and of genes involved in autism and intellectual disability.
  3. The findings from the experimental studies were used to develop new principles for risk assessment of this mixture.

“It is striking that the findings in the experimental systems well reflected what we found in the epidemiological part, and that the effects could be demonstrated at normal exposure levels for humans,” said Joëlle Rüegg, professor of environmental toxicology at Uppsala University.

“Human brain organoids (advanced in vitro cultures that reproduce salient aspects of human brain development) afforded, for the first time, the opportunity to directly probe the molecular effects of this mixture on human brain tissue at stages matching those measured during pregnancy. Alongside other experimental systems and computational methods, we found that the mixture disrupts the regulation of genes linked to autism (one of whose hallmarks is language impairment), hinders the differentiation of neurons and alters thyroid hormone function in neural tissue,” said Giuseppe Testa, principal investigator of the EDC-MixRisk responsible for the human experimental modelling.

“One of the key hormonal pathways affected was thyroid hormone. Optimal levels of maternal thyroid hormone are needed in early pregnancy for brain growth and development, so it’s not surprising that there is an association with language delay as a function of prenatal exposure,” said Barbara Demeneix, professor of physiology and endocrinology at the Natural History Museum in Paris.

By combining these techniques, the researchers were able to show that 54% of children included in the SELMA study were at risk of delayed language development (at age 30 months) as they were prenatally exposed to a mixture of chemicals at levels that were above the levels predicted to impact neurodevelopment. Yet this risk fell below the exposure limits for individual chemicals.

Source: EURION Cluster

Categories : Neurology Obstetrics & GynaecologyTags :

Reduced Antiepileptic Drug Effectiveness in Pregnancy Uncovered

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Blood levels of many commonly used antiepileptic drugs drop dramatically with the onset of pregnancy, which can result in ‘breakthrough seizures’ according to a study published in JAMA Neurology.

The findings, collected as part of the multicentre study Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD), explain why many people with epilepsy start experiencing breakthrough seizures after conception, underscoring the need to increase antiseizure medication doses and closely monitor blood levels over the course of pregnancy.

A fine-tuned medication regime is critical in epilepsy. “Some people mistakenly believe that changes in the drugs’ blood concentration won’t occur until after 20 weeks of pregnancy, but our study shows how important it is to start monitoring and adjusting patients’ medication dosages early on,” said lead author Dr Page Pennelll. “Nearly half of all pregnancies in the United States are unplanned, so it is important to ensure that doctors have a clear picture of each patient’s baseline drug level even if they are not trying to conceive.”

A life-altering neurological condition, two-thirds of epilepsy cases do not have a known cause. In people with epilepsy, nerve cells in the brain are hyper-reactive, causing them to change the pattern of their electrical activity and become spontaneously active. That synchronous activation is manifested in seizures.

Epilepsy has a fraught history of diagnosis and management; people with epilepsy go undiagnosed or under-treated. First-generation drugs to control it had many dangerous side effects and were contraindicated for people who are trying to conceive.

Since then, safer medications have entered the U.S. market and become widely available, but clinicians started noticing a new problem – patients whose epilepsy was successfully managed with medications started having seizures soon after becoming pregnant.

“Identifying which antiseizure medications may have changes in concentrations and at what point in pregnancy those changes occur is important for determining which patients may need to be monitored more closely during pregnancy and after delivery,” said senior author Professor Angela Birnbaum at the University of Minnesota.

To solve the mystery, the researchers embarked on a study to analyse blood concentrations of 10 commonly used antiseizure drugs and compare them across different stages of pregnancy and after childbirth.

The study found that blood levels of seven out of 10 of the medications they examined dropped dramatically — from 29.7% for lacosamide, a commonly prescribed anticonvulsant, and up to 56.4% for lamotrigine.

In addition, the researchers noted that the drop in drug levels occurred mere days after conception.

Source: University of Pittsburgh