During the 1918 flu pandemic, an estimated 20% of the world's population became infected and 50 million of those infections proved to be fatal. In the United States, the average lifespan dropped by 12 years per person. [ 10 ]  The disease struck indiscriminately by class but was often fatal for those that were in their 20s and 30s while having a particularly strong effect on pregnant women, infecting one third of all American women that were pregnant between 1918 and 1919. [ 1 ]  Children who were born in 1919 and had mothers who were infected during gestation experienced many handicaps later in life. Those born in 1919 experienced a 5% or more wage drop and were often found to have lower educational achievement overall. These children were also 20% more likely to be disabled than other comparable cohorts (early 1918 and late 1919) who did not experience in utero exposure. [ 1 ]  In a study conducted in 2008 it was found that in utero exposure to the pandemic led to higher chances of developing coronary heart disease and kidney disease later in life. The study concluded an 11.8% increased chance of coronary heart disease for those born in the first quarter of 1919. and a 51% increased chance of developing kidney disease for those born in the fourth quarter in 1918 as compared to those born in early 1918 and late 1919. It is also notable that those who were already born but young (between the ages of 1 and 5) during exposure did not have a noticeable increase in coronary heart disease or kidney disease. [ 11 ]  In Italy, one of the countries most affected by the pandemic, there was a drop in educational attainment for those in utero during exposure to the pandemic. Being exposed to the pandemic while in utero would lead to an average loss of 0.3–0.4 years of schooling. These effects were much higher or lower depending on the district of Italy. [ 12 ]  The possibility that maternal exposure to influenza during gestation may be linked to increased rates of schizophrenia later in life for the child. In a recent [ when? ]  study conducted in California they were able to predict schizophrenia in adult offspring by analyzing the influenza antibodies of pregnant women in 1959–1966. It has been hypothesized that a definite link exists between influenza-induced stress on the fetus and schizophrenia. [ 13 ]


During World War II, a Nazi barricade resulted in a severe famine in the Western Netherlands. Where food was previously plentiful, supplies immediately were cut off in November 1944, resulting in a period of starvation that lasted until spring of 1945. The Dutch people survived on as little as 30% of their daily needed caloric intake, and tens of thousands of people died. Analyses of the orderly health records from this time period allow for a systematic comparison of the effects of fetal starvation. Individuals who were in utero during the  Hunger Winter  were subject to different outcomes depending on the period of time in which they were conceived. Those who were in the first trimester during the three-month siege were likely to be born normal size, having caught up with typical development. However, these normal size babies developed high blood pressure, diabetes, and obesity. Contrary to this group, those who were in the third trimester during the siege, who presumably had been well nourished up until the last few months of gestation, were born small. But, these small babies stayed small their entire lives, and did not develop higher rates of obesity or disease. Surprisingly, effects continued to be seen in the offspring of the individuals who were fetuses at the time of the famine. [ 14 ]


During  Ramadan  (of the lunar cycle) many Muslims around the world participate in a fast during the daylight hours of the lunar month. This fasting usually entails abstaining from food or drink for the daylight hours of the month. There are groups that are automatically exempt from having to participate such as the young, sick and old but the list of exemption does not officially include pregnant women (though they are most often allowed exemption). The majority of pregnant women however, choose to participate despite the hardship due to cultural and personal pressure. [ 15 ]  In several recent studies on the effects of fasting during Ramadan and Fetal Origins Hypothesis they have found many negative outcomes on children who were in utero during the fast. These outcomes were as numerous as a change in birth weight to the long term health of the affected. The studies were conducted primarily in Uganda and Iraq but had some smaller sections in Michigan and other places for control groups or specific studies. The effects on birth weight are negatively correlated with Ramadan fasting. Arab Muslim pregnancies that overlap with the Ramadan fast experienced a lower birth weight of 18 grams per child. The effect was slightly larger at a lower birth weight of 20-25 grams if Ramadan fell somewhere in the first or second trimester of the pregnancy. [ 15 ]  In utero exposure to Ramadan fasting has a negative effect on male birth rate causing a skewed sex ratio for total births. When exposure to the Ramadan fast takes place a month after conception it is correlated with a 13% decline in total births. The effects on exposed males and females is drastically different where the male birth rate drops by 26% the female birth rate only drops by 2.5% leading to the assumption that "male vulnerability" may be to blame. [ 15 ]  In a study conducted in Uganda and Iraq on the levels of disability among those exposed to the fast while in utero they concluded that disability rates were much higher for those exposed when controlling for outside factors. Though the measure for disability differs by country the effect is still noticeable. For those born 9 months after Ramadan the likelihood of disability is higher than the surrounding population. The mean rate of disability in Uganda is 3.8% for the country but for those exposed the number is drastically higher at 22% mean disability rate. A similar effect can be observed in Iraq where the mean rate of disability is 1.5% but the disability rate of those exposed is 23%. [ 15 ]  In Uganda the recorded number of blind and deaf can be specifically recorded allowing one to see the effect on this specific disability to expose. Those born 9 months after Ramadan were 33% more likely to be blind and 64% more likely to be deaf than those not exposed in utero. The effects of exposure to the Ramadan fast can even be observed in mental disorders. In a study conducted in Uganda it was concluded that exposure to the fast, early in a pregnancy effectively doubles the likelihood of a person having a cognitive disorder of some kind. A similar discovery was made in Iraq where 63% higher likelihood of a cognitive disorder relative to the mean was discovered for all those exposed. [ 15 ]  Certain specific health effects have been observed for those exposed to in utero fasting. The reported signs of Anemia among the old were higher for those exposed during mid gestation, all other points in the gestation period were found to be insignificant. Anemia is caused by damage to the kidneys so the findings are consistent that the effect is noticeable during mid-gestation when the kidneys are developing. [ 16 ]


The offspring of  Holocaust  survivors have been found to have an epigenetic 'tag' change in their DNA similar to those of their parents, individuals affected directly by the Holocaust. This finding shows that gene expressions can be altered via stressful experiences and then passed down to children through prenatal conditions. While the children of the Holocaust survivors had not themselves experienced Nazi inflicted trauma, they experienced the physiological and emotional trauma as if they had. When compared to Jewish families who were living outside of affected areas of Europe, the findings continued to stand: "The gene changes in the children could only be attributed to Holocaust exposure in the parents." [ 17 ]


Pollution may affect the health of the mother, or cross over the placenta and enter the developing fetus. Beate Ritz, a professor at UCLA, found significantly higher rates of heart malformations and valve defects in the children born to women living in highly polluted areas of Los Angeles. [ 18 ]


Maternal stress has been linked to a number of negative outcomes for the developing fetus. Pregnant women who firsthand experienced the devastation of the World Trade Center attack on  September 11, 2001  were studied to observe the effects of PTSD (post-traumatic stress disorder) on their child's future health. Of the women studied, those who developed PTSD following the attacks had lower basal cortisol levels than a control group. Their children, also, had lower basal cortisol levels than those not exposed to extreme prenatal stressors. The finding was strongest for the women who were in their third trimester during 9/11. Based on the findings that there was a trimester distinction in strength, conclusions can be drawn that the development of a vulnerability to stress was due at least in part to environment in utero. [ 2 ]  9/11 is also correlated with lower birth weights of children born to women with Arabic sounding names following the attacks; this could possibly be due to fear of retaliation or stereotyping associations with the attackers. [ 19 ]  Stress has also been linked to preterm birth, as shown by research studies conducted following the  Tarapaca, Chile earthquake  in 2005, as well as the  Northridge, California earthquake  in 1994. [ 20 ]  Similar findings have been replicated for stressful life experiences and fetal outcomes in the  Hurricane Katrina  population of 2005. Women in New Orleans at the time who reported enduring multiple severe disaster experiences also had a significantly higher chance of delivering early or low birth weight children. [ 21 ]  Experiencing loss during pregnancy also influences postnatal outcomes. Women who experienced the death of a close family member, friend, or spouse, or were pregnant during a wartime conflict, were more likely to have children prematurely, and the children of these women were significantly more likely than the general population to suffer from schizophrenia in adulthood. [ 19 ] [ 22 ]  Besides birth weight, mental health, and reduced cortisol levels, effects of stress during pregnancy have also been linked to impaired cognitive development in children as seen in the maternal population exposed to a severe snowstorm in Canada. [ 23 ]  Women who experienced the most stressful storm related events had children with detriments in cognitive, language, behavioral, and attention outcomes. [ 23 ]  Shockingly, the poorer performance by these children has persisted until the age of ten. [ 23 ]  Even job-related stress has been found to be associated with low birth weight and preterm birth. Working long hours, having temporarily employment, or reporting physically demanding job tasks showed "significant and strong" associations with poorer later birth outcomes. [ 24 ]  Findings for the job stress-birth association have been replicated by obstetricians at Cedars-Sinai Medical Center in Los Angeles. [ 2 ]  However, some research has found that moderate amounts of stress and cortisol passed on to a developing fetus are actually beneficial, perhaps acting to give organs a "workout" prior to birth. [ 2 ]  Further cementing the theory that maternal emotional state can impact child development are the sound research findings that women who are clinically or slightly depressed during pregnancy are more likely to have children with low birth weight, putting them at risk for future health concerns of their own. [ 25 ]  On May 12, 2008, a raid took place in Postville, Iowa, where 389 workers at a meat processing factory were arrested and held for questioning. Out of the 389 workers detained, 270 served sentences and most were deported to primarily Mexico and Guatemala. [ 26 ]  Among those arrested 98% were Latino as they were suspected of being illegal immigrants. Latino families feared future deportations and future raids creating psychological stress on Latinos in the area. In relation to maternal stress a study was conducted which found that Latino babies born 37 weeks after the event experienced a 24% greater risk of lower birth (about 5.5 pounds) weight than babies born in other years. [ 27 ]  The risk for preterm births was also higher for Latina women when compared to non-Latina White women. [ citation needed ]


Criticism of the fetal origins hypothesis can be aimed at the limitations of the research. Confounds abound due to the intertwined nature of environment before and after birth, as well as the correlational factors associated with poverty outcomes. Additionally, the use of historical and longitudinal data raises the question of reliability. [ 28 ]  Also, some critics maintain that despite the compelling relationship documented between low birth weight and later disease, it is too soon to begin to mandate interventions aimed at increasing birth weight. Such interventions could instead have increased negative effects, [ 29 ]  until the specific mechanisms and processes are more deeply understood by which birth and early childhood weight determine development. As stated in "Killing Me Softly: The Fetal Origins Hypothesis", "Such pre-emptive targeting would constitute a radical departure from current policies that steer nearly all healthcare resources to the sick, i.e. the "pound of cure" approach. That said, the existing evidence is not sufficient to allow us to rank the cost-effectiveness of interventions targeted at women against more traditional interventions targeted at children, adolescents, or adults. For example, broadening the target population to women who might get pregnant would reduce the set of policies which are cost effective." [ 1 ]


The implications of the  Developmental Origins of Health and Disease  hypothesis are akin to changing the focus of public health intervention from childhood to in utero. Because the demonstrated effects range from dramatic to subtle in the wide spread areas of educational achievement, emotional stability, career trajectory, life expectancy, disease prognosis, and psychological disorders, interventions addressing the gestational period could potentially have significant impact on individual and societal levels. Proposed and in effect interventions include the following:


Fetal programming , also known as  prenatal programming , is the theory that environmental cues experienced during fetal development play a seminal role in determining health trajectories across the lifespan.


Three main forms of programming that occur due to changes in the maternal environment are:


These changes in the maternal environmental can be due to nutritional alteration, [ 1 ]  hormonal fluctuations [ 2 ]  or exposure to toxins.


In 1944–45, the German blockade of the Netherlands led to a lack of food supplies, causing the  Dutch famine of 1944–45 . The famine caused severe malnutrition among the population, including women in various stages of pregnancy. The Dutch Famine Birth Cohort Study examined the impact of lack of nutrition on children born during or after this famine. It showed that over the course of their life, these children were at greater risk of  diabetes ,  cardiovascular disease ,  obesity , and other  non-communicable diseases . [ citation needed ]


In the 1980s,  David Barker  began a research study on this topic. The Barker Hypothesis, or  Thrifty phenotype , forms the basis for much of the research conducted on fetal programming. This hypothesis states that if the fetus is exposed to low nutrition, it will adapt to that particular environment. Nutrients are diverted towards the development of the heart, brain, and other essential organs of the fetus. The body also undergoes metabolic alterations that ensure survival in spite of low nutrition but may cause problems in situations with normal or high nutrition. [ 3 ]  This leads to increased risk of  metabolic syndrome .


The developing fetus forms an impression of the world into which it will be born via its mother's nutritional status. Its development is thus modulated to create the best chance of survival. However, excessive or insufficient nutrition in the mother can provoke maladaptive developmental responses in the fetus, which in turn manifest in the form of post-natal diseases. It is possible that this has such a profound effect on the fetus’ adult life that it can even outweigh lifestyle factors. [ 1 ]


Body mass index  prior to pregnancy and weight gain during pregnancy are both linked to high blood pressure in the offspring during adulthood. Mouse models suggest that this is due to high levels of the fetal hormone  leptin , which is present in the blood of individuals that are overweight or obese. There is a theory that this hormone has a negative impact on the regulatory systems of the fetus, and renders it impossible to maintain normal blood pressure levels. [ 4 ]


Pre-eclampsia , involving oxygen deprivation and death of  trophoblastic cells  that make up most of the placenta, is a disease which is often associated with maladaptive long-term consequences of inappropriate fetal programming. Here, an inadequately developed and poorly functioning placenta fails to meet the fetus’ nutritional needs during gestation, either by altering its selection for nutrients which can cross into fetal blood or restricting total volume thereof. Consequences of this for the fetus in adult life include cardiovascular and metabolic conditions. [ 5 ]


A delicate balance of hormones during pregnancy is regarded as being highly relevant to fetal programming and may significantly influence the outcome on the offspring. [ 6 ]  Placental endocrine transfer from the mother to the developing fetus could be altered by the mental state of the mother, due to affected  glucocorticoid  transfer that takes place across the placenta. [ 6 ]


Thyroid hormones play an instrumental role during the early development of the fetus's brain. Therefore, mothers suffering from thyroid-related issues and altered thyroid hormone levels may inadvertently trigger structural and functional changes in the fetal brain. The fetus is able to produce its own thyroid hormones from the onset of the second trimester; however, maternal thyroid hormones are important for brain development before and after the baby is able to synthesize the hormones while still in the uterus. [ 7 ]  Due to this, the baby may experience an increased risk of neurological or psychiatric diseases later in life. [ 7 ]


Cortisol (and glucocorticoids more generally) is the most well studied hormonal mechanism that may have prenatal programming effects. [ 8 ]  Although cortisol has normative developmental effects during prenatal development, excess cortisol exposure has deleterious effects on fetal growth, [ 9 ]  the postnatal function of physiological systems such as the hypothalamic-pituitary-adrenal axis  [ 10 ]  and brain structure or connectivity (e.g., amygdala). [ 11 ] [ 12 ]


During gestation, cortisol concentrations in maternal circulation are up to ten times higher than cortisol concentrations in fetal circulation. [ 13 ]  The maternal-to-fetal cortisol gradient is maintained by the placenta, which forms a structural and enzymatic barrier to cortisol. [ 14 ] [ 15 ]  During the first two trimesters of gestation intrauterine cortisol is primarily produced by the maternal adrenal glands. [ 16 ]  However, during the third trimester the fetal adrenal glands begin to endogenously produce cortisol and become responsible for most intrauterine cortisol by the time the fetus reaches term. [ 16 ]


Mental state of the mother during pregnancy affects the fetus in the uterus, predominantly via hormones and genetics. [ 17 ]  The mother's mood, including maternal prenatal anxiety, depression and stress during pregnancy correlates with altered outcomes for the child. [ 17 ]  That being said, not every fetus exposed to these factors is affected in the same way and to the same degree, and genetic and environmental factors are believed to have a significant degree of influence. [ 17 ]


Maternal depression poses one of the greatest risks for increased vulnerability to adverse outcomes for a baby that is developing in the uterus, especially in terms of susceptibility to a variety of psychological conditions. [ 18 ]  Mechanisms that may explain the connection between maternal depression and the offspring's future health are mostly unclear and form a current area of active research. [ 18 ]  Genetic inheritance that may be rendering the child more susceptible may play a role, including the effect on the intrauterine environment for the baby whilst the mother suffers from depression. [ 18 ]


Maternally experienced psychological stress that occurs either prior to or during gestation can have intergenerational effects on offspring. Stress experienced during gestation has been linked with preterm delivery, low birth weight, and increased risk of psychopathology. [ 6 ]  The new mother may suffer from after-effects too, such as postpartum depression, and subsequently may find parenting more difficult as compared to those who did not experience as much stress during their pregnancies. [ 6 ]


Toxins such as alcohol, tobacco and certain drugs to which the baby is exposed to during its development are thought to contribute to fetal programming, especially via alterations to the HPA axis. [ 19 ]  If the exposure occurs during a critical phase of fetal development, it could have drastic and dire consequences for the fetus. [ 19 ]


Prenatal and/or early postnatal exposure to alcohol (ethanol) has been found to have a negative effect on child's neuroendocrine and behavioral factors. [ 20 ]  Alcohol passes through the placenta on being ingested by the mother during her pregnancy, and makes its way to the baby  in utero . [ 20 ]  Changes posed to the fetus through ethanol exposure may significantly effect growth and development; these are collectively known as fetal alcohol spectrum disorders (FASD). [ 20 ]  The exact interaction between ethanol and the developing fetus is complex and largely uncertain, however, several direct and indirect effects have been observed as the fetus matures. [ 20 ]  Predominant among these are irregularities in the fetus's endocrine, metabolic and physiological functions. [ 20 ]


The negative consequences of  smoking  are well-known, and these may be even more apparent during pregnancy. [ 17 ]  Exposure to tobacco smoke during pregnancy, commonly known as  in utero  maternal tobacco smoke exposure (MTSE), can contribute towards various problems in babies of smoking mothers. [ 17 ]  About 20% of mothers smoke whilst pregnant and this is associated with increased risk of complications, such as preterm birth, decreased fetal growth leading to lower birth weight, and impaired fetal lung development. [ 17 ]


There is evidence pointing towards pharmacological programming of the fetus during the first trimester. [ 21 ]  One type of drugs which is suspected of influencing the developing baby when used during pregnancy is anti-hypertensive drugs. [ 21 ]  Pre-eclampsia (a condition of hypertension during pregnancy), is a serious problem for the majority of pregnant mothers and can predispose the mother to a variety of complications, including increased risk of mortality and problems during parturition. [ 21 ]


A  gender reveal party  is a  party  held during  pregnancy  to reveal the baby's  sex  to the expectant parents' family and friends, and sometimes to the parents themselves.  Prenatal sex discernment  technology furnishes the necessary information. [ 1 ] [ 2 ]  The practice originated in the United States during the late 2000s. [ 2 ]


It is distinct from, but sometimes combined with, a  baby shower , where the primary activity is giving expecting parents gifts for their future child. The gender reveal party often involves  gender stereotypes  such as  pink and blue  denoting girls and boys, respectively. [ 1 ] [ 2 ]


The practice has been criticized for the use of elaborate and dangerous special effects, which have directly contributed to multiple deaths, injuries and large-scale forest fires, namely the  2017 Sawmill Fire  and the  2020 El Dorado Fire . [ 3 ] [ 4 ]  The practice has also been criticized for reinforcing  gender stereotypes  and the  gender binary . [ 1 ] [ 2 ] [ 5 ]


The gender reveal party developed in the late 2000s. An early example was recorded in the 2008 posts of Jenna Karvunidis on her  ChicagoNow   blog   High Gloss and Sauce  announcing the sex of her fetus via a cake; she had previously had several miscarriages and wished to celebrate that her pregnancy had developed to the point that the sex of the fetus could be determined. [ 6 ] [ 7 ]   YouTube  videos can be found as early as 2008 and 2009, becoming significant around 2011, after which the trend continued to grow through the 2010s. [ 8 ] [ 2 ]


In 2019, Karvunidis observed an increase in extreme reveal events over the preceding five years, with parents "burning down forests and exploding cars, bringing alligators into the mix". She expressed regret at having helped start the trend, learning how the  LGBT  and  intersex  communities feel, and finally revealing the daughter they announced back in 2008 to be a  gender-nonconforming  individual who wears suits while still identifying as female. [ 6 ]  After the 2020  El Dorado Fire  was started by a malfunctioning pyrotechnical device at a gender reveal party, Karvunidis pleaded for people to stop staging such events. [ 9 ]


Baby showers , a traditional prenatal celebration, have some key differences from gender reveal parties. Primarily, the focus on gender reveal parties is the fetus' sex, while baby showers focus on the giving of supplies and items for the future infant to expectant parents. Traditionally, baby showers are for  women only , while gender reveal parties have no inherently-associated gender restriction. [ citation needed ]  Some couples combine the two. [ 1 ] [ 2 ]


This trend was popularized on  social media  platforms such as YouTube,  Instagram , and  Pinterest , although it originated before the latter two. [ 8 ] [ 5 ]  This  mediatization  has significantly boosted the likelihood of expectant parents to have or take part in gender reveal parties. Internet  remix culture  lends the practice great receptivity toward  individual creativity , a factor in their growing popularity. [ 1 ] [ 2 ]  Demographic research shows the most gender reveal parties are done by expecting parents that are  middle-class ,  heterosexual   White Americans  who are  married  or  partnered . [ 1 ]


The trend has also reached  South Korea . In 2022, Na Ju-ye of the  Hankook Ilbo  reported that the trend was growing amongst young parents. Na noted that the parties differed in several ways from those in the West. Some parties, instead of focusing on the parents, are focused on the grandparents. In addition, due to the  low birth rate in South Korea , the parties are perceived somewhat positively and the historical practice of preferring male children has become significantly reduced. Finally, while there is technically a law that forbids doctors from informing parents of a baby's gender before 32 weeks of pregnancy, parents still manage to receive guesses from doctors. [ 10 ]


The focus of gender reveal parties being the fetal sex,  such information  is a prerequisite. This can be determined at or after the  gestational age  required by the method being used. For  ultrasound , the most common method, the earliest this can be reliably done is approximately 65 days, but it is typically done at around 20 weeks. [ a ]  Both the determination of fetal sex and the party are typically held during the  second trimester . [ 1 ] [ 11 ]


Post-examination knowledge of the fetal sex by the parents varies. Most commonly, a third party (sometimes called a "gender guardian") is entrusted with the information, and it remains a secret from the parents until the reveal. This person is responsible for making party arrangements to ensure the reveal happens without the prior knowledge of the parents. In other cases, it is already known to one or both parents, and the reveal is specifically for attendees. [ 1 ]


To help maintain the mystery, party decorations are typically heavily gendered, but  ambiguous  when taken as a whole. [ 1 ]


While the focus remains on the fetal sex, the reveal is typically the climax of the party. Prior to the reveal,  party games  are common, in which attendees or expecting parents guess or assert the fetal sex. [ 1 ]  This can also take the form of  competition  between a "Team Pink" and "Team Blue" which parents or participants may join. [ 1 ] [ 2 ]


Sometimes the event includes features of a baby shower. If this is the case, gifts may be given or opened at a specific time. [ 1 ] [ 2 ]


Most reveal methods utilize  gender-associated  colors, most typically  blue  and  pink  representing  male  and  female  respectively, decorated with other gender-associated items. The method of reveal varies; common methods involve cutting  special cakes , launching or popping  balloons ,  confetti , streamers,  piñatas ,  colored smoke , and  Silly String . Other seasonally-related items such as  Easter eggs ,  Jack-o'-lanterns ,  Christmas presents , or  Fourth of July  or  New Year's   fireworks  may also be incorporated depending on time of pregnancy. [ 1 ] [ 2 ]


Once these colors are revealed, both the expecting parents and onlookers are made aware of the fetus's sex, typically to great celebration and comment by attendees. The  announcement of a predetermined, sex-dependent baby name  may also take place. [ 1 ]


The term "gender reveal" is considered a  misnomer  by those who believe in a  distinction between sex and gender . [ 2 ]  In this view, gender is a  social construct  and impossible to  determine from biological characteristics . Thus, when the "gender reveal" is made, it is the  sex  and not the gender that is being revealed. [ 2 ] [ 8 ] [ 12 ] [ 13 ] [ 14 ]  Although some have argued renaming the concept to a "sex reveal party", the title has failed to catch on. [ 14 ] [ 15 ] [ 16 ]


Furthermore, gender reveal parties rely heavily on the assumption that the child will not be  intersex , which occurs in an estimated 1 in 4,500–5,500 births. [ 17 ] [ 18 ]  Gender reveal parties have been argued to reinforce  gender essentialism , precluding and minimizing  transgender  identity. [ 8 ] [ 15 ] [ 17 ]  Some parents have rejected gender reveal events, in part because of conversations regarding gender identity and transgender issues becoming more common. [ 5 ]


Overall, the practice reinforces stereotypical  gender roles , often utilizing polarizing gender dichotomies in party materials such as "Guns or Glitter", "Pistols or Pearls", or "Wheels or Heels". [ 1 ] [ 2 ] [ 14 ] [ 15 ]  Critics say that there is no reason to assume a neat fit into the essentialist dichotomy even in the case of a cisgender, non-intersex child. [ 5 ] [ 13 ] [ 17 ]  In 2019, Jenna Karvunidis, considered one of the pioneers of gender reveal parties, called for re-evaluation of the practice due to how it might affect  transgender  and  non-binary  individuals, writing about her own daughter's  gender nonconformity . [ 6 ] [ 7 ]


The practice has also been criticised for sometimes involving dangerous stunts [ 16 ] [ 19 ]  and animal abuse. [ 20 ]  After the  El Dorado Fire  in 2020, Karvunidis decried the parties and pleaded for people to stop having them. [ 9 ]


Some instances of attempted spectacular  special effects  at gender reveal events have caused injury, death, and large-scale damage:


Some families of transgender people host gender reveal parties for transgender family members who come out during these parties. [ 34 ] [ 35 ]


Gestational hypertension  or  pregnancy-induced hypertension  ( PIH ) is the development of new  hypertension  in a  pregnant  woman after 20 weeks' gestation without the presence of protein in the urine or other signs of  pre-eclampsia . [ 1 ]  Gestational hypertension is defined as having a blood pressure
greater than 140/90 on two occasions at least 6 hours apart. [ 1 ]


No single diagnostic test currently exists to predict the likelihood of developing gestational hypertension. High blood pressure is the major sign in diagnosing gestational hypertension. Some women with gestational hypertension may present asymptomatic, but a number of symptoms are associated with the condition. [ 2 ]


Symptoms


Maternal causes


Pregnancy


Family history


There exist several  hypertensive states of pregnancy :


Pre-eclampsia and eclampsia are sometimes treated as components of a common syndrome. [ 6 ]


There is no specific treatment, but is monitored closely to rapidly identify pre-eclampsia and its life-threatening complications ( HELLP syndrome  and eclampsia). [ citation needed ]


Drug treatment options are limited, as many  antihypertensives  may negatively affect the  fetus .  ACE inhibitors ,  angiotensin receptor blockers , and  direct renin inhibitors  are contraindicated in pregnancy as they are  teratogenic .  Methyldopa ,  hydralazine ,  nifedipine , and  labetalol  are most commonly used for severe pregnancy hypertension. [ 7 ]


The fetus is at increased risk for a variety of life-threatening conditions, including  pulmonary hypoplasia  (immature lungs).  If the dangerous complications appear after the fetus has reached a point of viability, even though still immature, then an early delivery may be warranted to save the lives of both mother and baby. An appropriate plan for labor and delivery includes selection of a hospital with provisions for advanced life support of newborn babies. [ citation needed ]


Exercise during pregnancy can help prevent hypertension as it can improve not only health for the mother but also the child. Exercise can regulate the energy needs required during pregnancy while also decreasing inflammation. Regular exercise can also lower the increased stress levels associated with pregnancy. [ 8 ]


There have been significant findings on how exercising can help reduce the effects of hypertension just after one bout of exercise. Exercising can help reduce hypertension as well as pre-eclampsia and eclampsia. There have been findings in recent studies suggesting that exercising according to recommended guidelines during pregnancy can reduce the risk of developing gestational hypertensive disorder by 30%.  [ 9 ]  The CDC recommends that during pregnancy, the pregnant women should exercise 150 minutes each week specifically focusing on aerobic activity at a moderate intensity.  [ 10 ]


The acute physiological responses include an increase in cardiac output (CO) of the individual (increased heart rate and stroke volume). This increase in CO can inadvertently maintain the amount of blood going into the muscles, improving functionality of the muscle later. Exercising can also improve systolic and diastolic blood pressure making it easier for blood to pump to the body. Through regular bouts of physical activity, blood pressure can reduce the incidence of hypertension.  [ 11 ]  A recent meta-analysis presented that exercise interventions in pregnant women could reduce both systolic and diastolic blood pressure. The meta-analysis study found that exercise is more likely to reduce the risk of hypertensive disorder of pregnancy in women who are more prone to developing hypertensive disorders of pregnancy.  [ 12 ]  Risk factors that influence the likelihood of developing hypertensive disorders of pregnancy include, a maternal age of 40 or more, pre-pregnancy obesity, excess weight gain during pregnancy and gestational diabetes.  [ 13 ]


Aerobic exercise has been shown to regulate blood pressure more effectively than resistance training. Compared to having a sedentary lifestyle, being physically active in aerobic exercise for 30-60 minutes 2-7 times a week significantly decreases the risk of gestational hypertension in pregnancy compared to a sedentary individual who is pregnant.  [ 14 ]  It is recommended to see the effects of exercising, that a person should aim for 5-7 days/ week of aerobic exercise. This type of exercise should have an intensity of light to moderate, utilizing ~85% of max heart rate (220-age). Aerobic has shown a decrease in SBP by 5-15mmHg, versus resistance training showing a decrease of only 3-5mmHg. Aerobic exercises such as jogging, rowing, dancing, or hiking can decrease SBP the greatest. The decrease in SBP can regulate the effect of hypertension ensuring the baby will not be harmed. Resistance training takes a toll on the cardiovascular system in untrained individuals, leading to a reluctance in prescription of resistance training for hypertensive reduction purposes.  [ 15 ]


Gestational hypertension is one of the most common disorders seen in human pregnancies. [ 16 ]  Though relatively benign on its own, in roughly half of the cases of gestational hypertension the disorder progresses into pre-eclampsia, a dangerous condition that can prove fatal to expectant mothers. [ 17 ]   However, gestational hypertension is a condition that is fairly rare to see in other animals.  For years, it has been the belief of the scientific community that gestational hypertension and pre-eclampsia were relatively unique to humans, although there has been some recent evidence that other primates can also develop similar conditions, albeit due to different underlying mechanisms. [ 16 ]  The underlying cause of gestational hypertension in humans is commonly believed to be an improperly implanted placenta.  Humans have evolved to have a very invasive placenta to facilitate better oxygen transfer from the mother to the fetus, to support the growth of its large brain. [ 18 ]


The origins of gestational hypertension may lie with the development of humans'  hemochorial  placenta.  A hemochorial placenta optimizes the amount of oxygen and nutrients that can be absorbed into the fetal blood supply, while at the same time ensuring rapid diffusion of wastes away from the fetus.  This hemochorial placenta differs from lower primates' epitheliochorial placentae in the way that it allows the fetal tissues to interact directly with the mother's blood.  The hemochorial placenta thereby promotes more rapid diffusion to and from the fetal blood supply. [ 19 ]


In animals with epitheliochorial placentae such as horses and pigs, the greatest resistance to maternal blood flow in the vascular system was found within the placenta.  However, in animals with hemochorial placental structures such as rodents and primates, the vascular resistance in the placenta was low, leading scientists to the conclusion that the greatest resistance to maternal blood flow is found elsewhere in the maternal vascular system. [ 20 ]   The high vascular resistance outside of the placenta leads to higher maternal blood pressure throughout the body. [ citation needed ]


The fetal cells that implant into the uterine wall are known as the trophoblast.  The hemochorial placenta bathes the fetal trophoblast in maternal blood by forming lacunae, or lakes, of the mother's blood that surround fetal tissue.  The lacunae are filled by the spiral arteries, which means that the mother's blood pressure is the driving force behind the introduction of new blood, which contains both oxygen and food for the fetus, to the system. [ 21 ]   It is thought that humans need the increased diffusion provided by the hemochorial placenta in order to grow the large brains compared to their body size that distinguish them from other primates. [ 22 ]


It is thought that "failings" in normal hemochorial placental structure lead to pre-eclampsia and gestational hypertension. [ 23 ]   The human placenta implants "earlier, deeper, and more extensively" into the uterine wall, which can potentially lead to many problems that are found in human pregnancies, but not as much in other animals.  Miscarriage and pre-eclampsia are both very rare in other species, but are two of the most common pregnancy-related diseases in humans. [ 24 ]  The genetic roots of gestational hypertension and pre-eclampsia are certain, as women with a family history of the condition are three times more likely to develop it when they are pregnant. [ 25 ]


One of the potential causes of gestational hypertension and pre-eclampsia is when the trophoblast does not invade far enough into the uterine lining. [ 26 ]   When the fetus's trophoblast does not fully extend into the uterine wall, the spiral arteries do not become fully converted into low-resistance channels. [ 24 ]   It has been found that this incomplete conversion of spiral arteries increases the resistance to uterine blood flow during pregnancy, and that this occurrence was associated with gestational hypertension. [ 27 ]   One potential cause of this incomplete breach of the spiral arteries that leads to gestational hypertension is a mistaken immune response by the maternal tissue, reaction to the alien fetal tissue. [ 28 ]   Therefore, it is clear that the complication of gestational hypertension has roots in the early implantation of the fetus in the uterine wall, an implantation technique that is unique to humans. [ citation needed ]


The highly invasive placenta that is found in humans is thought to be linked to humans' high circulating levels of the hormones CG and hCG. It has been shown that the higher the levels of these hormones, the deeper the trophoblast's invasion into the uterine wall.  Instances of gestational hypertension and pre-eclampsia have been shown to occur when the invasion of the uterine wall is not deep enough, because of lower CG and hCG levels in the mother. [ 29 ]


Despite these risks for gestational hypertension, the hemochorial placenta has been favored because of its advantages in the way that it aids in diffusion from mother to fetus later in pregnancy.  The bipedal posture that has allowed humans to walk upright has also led to a reduced cardiac output, and it has been suggested that this is what necessitated humans' aggressive early placental structures. [ 30 ]   Increased maternal blood pressure can attempt to make up for lower cardiac output, ensuring that the fetus's growing brain receives enough oxygen and nutrients. [ 29 ]   The benefits of being able to walk upright and run on land have outweighed the disadvantages that come from bipedalism, including the placental diseases of pregnancy, such as gestational hypertension.  Similarly, the advantages of having a large brain size have outweighed the deleterious effects of having a placenta that does not always convert the spiral arteries effectively, leaving humans vulnerable to contracting gestational hypertension.  It is speculated that this was not the case with Neanderthals, and that they died out because their cranial capacity increased too much, and their placentae were not equipped to handle the fetal brain development, leading to widespread pre-eclampsia and maternal and fetal death. [ 31 ]


Gestational hypertension in the early stages of pregnancy (trimester 1) has been shown to improve the health of the child both in its first year of life, and its later life. [ 32 ]   However, when the disease develops later in the pregnancy (subsequent trimesters), or turns into pre-eclampsia, there begin to be detrimental health effects for the fetus, including low birth-weight. [ 17 ]  It has been proposed that fetal genes designed to increase the mother's blood pressure are so beneficial that they outweigh the potential negative effects that can come from pre-eclampsia. [ 32 ]  It has also been suggested that gestational hypertension and pre-eclampsia have remained active traits due to the cultural capacity of humans, and the tendency for midwives or helpers to aid in delivering babies. [ 33 ]


It is the goal of  evolutionary medicine  to find treatments for diseases that are informed by the evolutionary history of a disease. It has been suggested that gestational hypertension is linked to insulin resistance during pregnancy. [ 34 ]   Both the increase in blood sugar that can lead to gestational diabetes and the increase in blood pressure that can lead to gestational hypertension are mechanisms that mean to optimize the amount of nutrients that can be passed from maternal tissue to fetal tissue.  It has been suggested that techniques used to combat insulin insensitivity might also prove beneficial to those with gestational hypertension. [ 34 ]   Measures to avoid insulin resistance include avoiding obesity before pregnancy, minimizing weight gain during pregnancy, eating foods with low glycemic indices, and exercising. [ 34 ]


Gestational weight gain  is defined as the amount of weight gain a woman experiences between conception and birth of an infant. [ 1 ]


The Institute of Medicine (IOM) recommendations for gestational weight gain are based on body mass index (BMI) of women prior to pregnancy. However, early first trimester BMI appears to be a valid proxy for pre-conception BMI. [ 2 ]  BMI is split up into four categories: underweight (<18.5 kg/m^2), normal weight (18.5-24.9 kg/m^2), overweight (25-29.9 kg/m^2), and obese (≥30.0 kg/m^2). [ 3 ]  The IOM has recommended the ranges of weight gain to be 12.5–18 kg, 11.5–16 kg, 7-11.5 kg, and 5–9 kg respectively. That is, the smaller the BMI pre pregnancy, the more weight a woman is expected to gain during her pregnancy. [ 3 ]


Excessive GWG (eGWG) has been shown to adversely affect maternal and baby health postpartum. [ 4 ]  Only a little over a quarter of women have adequate GWG, meaning that their weight gain during pregnancy falls within the IOM recommended range. A little less than a quarter of women have inadequate GWG. However, excessive GWG is the most prevalent occurring in around half of pregnant women. [ 4 ] [ 5 ] [ 6 ] [ 7 ]


Having a higher BMI pre-pregnancy may leave one at a greater risk for excessive gestational weight gain and ultimately for cardio-metabolic diseases prenatally and postpartum. [ 7 ] [ 8 ] [ 9 ]


Food security  is defined as consistent access, geographically or financially, to sufficient, nutritious, and affordable food and has been theorized to be a cause of excess gestational weight gain. [ 7 ]  Women that only have access to fast food, for example, would be considered to be "lower food security", and these women might be more likely to suffer from excess gestational weight gain because the food available is cheap, but high in calories. [ 7 ] [ 4 ] [ 10 ]  Having access to affordable and nutritious food has been linked to a lesser risk of impaired glucose tolerance. [ 10 ]  which is related to excess gestational weight gain. [ 11 ]


It is not uncommon for there to be a correlation between socioeconomic status and food security; that is, women of low socioeconomic status have been reported to have low food security, particularly in terms of the affordability of nutritious food. [ 7 ]  Some women of low socioeconomic status claim that they feel pressure to eat more during pregnancy out of the fear that they are not providing their babies with enough food. [ 7 ] [ 12 ]  With low food security, these women would consume high calorie food in significant quantities, potentially leading to excess gestational weight gain. [ 7 ]  There seems to be a negative correlation between food security and excess gestational weight gain that is sometimes related to socioeconomic status. [ citation needed ]


Overweight and obese women are significantly more likely to expect excessive gestational weight gain compared with normal-weight women, and women who report expecting to gain excessively are three times more likely to actually gain excessively  than those who expect to gain within the guidelines. [ 13 ]


Regardless of a relation to food security, having a low income might also predispose women to excess gestational weight gain, yet the reasoning is unclear. [ 10 ]  One possibility is related to stress. Financial stress has been shown to be positively correlated with levels of CRP postpartum, a stress hormone associated with weight gain most likely because people eat increasingly unhealthy when stressed. [ 14 ]  Women with a higher monthly budget for food may have a healthier gestational weight gain, while those with less money allocated for food may be more likely to experience excessive gestational weight gain. [ 15 ]  However, the opposite may also be true: wealthier women may be more likely to suffer from excess gestational weight gain. [ 4 ] [ 10 ]  Women in wealthy communities have been reported to have higher postpartum weight retention than those in more poverty, [ 10 ]  and since women who have excessive gestational weight gain are more likely to retain weight postpartum [ 16 ] [ 17 ]  women in less poverty might be more likely to have excess gestational weight gain. [ 4 ] [ 10 ]  This suggests that a greater household income does not necessarily provide protection against excess gestational weight gain. [ citation needed ]


Race/ethnicity is an important variable to take into account when discussing gestational weight gain because women of racial/ethnic minorities demonstrate disproportionately higher obesity levels than non-Hispanic white women. [ 8 ] [ 18 ]  The IOM guidelines were created from data mostly consisting of white women, and thus may not be an appropriate measure for women of other races/ethnicities. [ 8 ]


African American women in general may have higher postpartum cardio-metabolic risk and more excess gestational weight gain than Latina women, who in turn have more than white women. [ 9 ]  However, this is not always the case. One study reported that although African American women are more likely to be overweight or obese pre-pregnancy, they were less likely to have excessive weight gain than white women in one study. [ 8 ]


Even though in many areas in the United States, there has been a decline in inequality on the basis of race/ethnicity, there still exists disproportionate social stratification. [ 4 ]  Racial/ethnic minorities, such as blacks and Latinos, are more likely to be found in neighborhoods high in poverty. [ 4 ] [ 9 ]  African American women in poverty have been seen to have significantly higher postpartum cardio-metabolic risk than wealthier African American women, [ 9 ]  which could be partially related to these impoverished women having excess gestational weight gain. [ 19 ]  White women in poverty, on the other hand, had excess gestational weight gain and higher postpartum cardio-metabolic risk than the white women with higher incomes. [ 4 ] [ 9 ]  This was also true for Latina women in poverty compared to those wealthier. [ 9 ]  The information regarding how race/ethnicity affects experience of excess gestational weight gain can be related to poverty levels, and the data available is limited and variable. [ citation needed ]


The  multigenic complex  formed by the human growth hormone ( hGH ) and the human placental lactogen (hPL) takes part in the process of maternal and fetal metabolism regulation and the following growth and development of the fetus. [ 1 ]


It is thought that from a gene duplication of an ancestral predecessor of the hGH, hPL was created. This procedure is related with the high homological similarity (approximately 95% similarity in  mRNA 's coding regions) between these two genes creating the hGH-hPL multigene family. Even though the genes have lots of similarities in their structures, they are expressed in different tissues. Later  mutations  in both genes sequence of  nucleotides  explain these differences among the GH group and the PL. [ 2 ]


The hGH-hPL multigene family is located in the 17th chromosome, concretely between the q22 and q24 regions occupying an approximately 50.000 pairs of nitrogen bases area. It is formed by 5 genes: two hGH and three hPL with a similarity between 91% and 95%:


The similarity of this five genes is shown in their function, as it has been exposed previously, but also in their structure. Each of them is formed by 5  exons  and 4  introns . Their length is also very similar. Moreover, the three hPL genes, which are all found in the placenta, contain an enhancer sequence (DNA sequence that increases the transcription levels in gene family). [ 3 ]


Regarding the intergenic space, this has a length between 6000 and 13000 pb (1pb, picobarn = 10 −36  cm 2 ). This space is filled with a serie of intergenic sequences repeated along the complex. The function of this sequences hasn't been clearly defined yet.


It has been demonstrated that hGH-hPL multigene interacts with different hormones during pregnancy and produces different proteic products which are secreted in the maternal and fetal circulations. This interaction starts in the 6th week of pregnancy and it has an important influence on the fetus growth.
In the pregnant woman it increases its  insulin-like growth factor  (IGF) sintesys which regulates the fetus metabolism, stimulating the production of  glucose  and amino acids.


Every gene in this multigene family produces a specific proteic product which has a great importance in the regulation of pregnancy, concretely in the correct embryo growth.


In the hGH-hPL complex, formed by 5 genes, there's only one gene which is not expressed in the placenta: the hGH-N gene, expressed in the hypophysis. This gene produces an  isoform  of 22 kilodaltons and another one of 20 kilodaltons. Both of them end up in the bloodstream with the other hormones coming from the pituitary gland.


The rest of the genes produce a set of peptides found in the placenta. On the one hand, the hGH-V gene produces two isoforms in different proportions: one of 22 kDa and the other one of 26 kDa. On the other hand, the hPL-3 and hPL-4 genes interact together secreting chorionic somatomammotropin, also called  placental lactogen . The proportion of each gene in this interaction depends on every individual and is different for every pregnancy, going from a 1:1 to a 1:6 proportion of hPL-3 and hPL-4.


Finally, the hPL-1 pseudogene doesn't have a proteic product. Firstly, it was thought that this gene was inactive and wasn't transcribed. However, some posterior studies showed a small presence of the hPL-1 gene in the placenta. The absence of a proteic product produced by this gene hasn't been explained yet though.


In pregnancies with complete lack of HPL and hGH-V in the placenta, the embryo suffers from a retarded growth; however, this is the only trascendental consequence and the embryo results on a healthy normal baby. The analysis in this cases show that HPL, hPL-4, hPL-3 and hGH-V genes were eliminated while hPL-1 remained intact. [ 4 ]


Intrauterine growth restriction  ( IUGR ), or  fetal growth restriction , is the poor  growth  of a  fetus  while in the  womb  during  pregnancy . IUGR is defined by clinical features of  malnutrition  and evidence of reduced growth regardless of an infant's  birth weight  percentile. [ 5 ]  The causes of IUGR are broad and may involve maternal, fetal, or placental complications. [ 6 ]


At least 60% of the 4 million  neonatal deaths  that occur worldwide every year are associated with  low birth weight  (LBW), caused by intrauterine growth restriction (IUGR), preterm delivery, and  genetic abnormalities , [ 7 ]  demonstrating that under-nutrition is already a leading health problem at  birth .


Intrauterine growth restriction can result in a baby being  small for gestational age  (SGA), which is most commonly defined as a weight below the 10th  percentile  for the  gestational age . [ 8 ]  At the end of pregnancy, it can result in a low birth weight.


There are two major categories of IUGR: pseudo IUGR and true IUGR [ citation needed ]


With pseudo IUGR, the fetus has a birth weight below the tenth percentile for the corresponding gestational age but has a normal ponderal index, subcutaneous fat deposition, and body proportion. Pseudo IUGR occurs due to uneventful intrauterine course and can be rectified by proper postnatal care and nutrition. Such babies are also called small for gestational age. [ citation needed ]


True IUGR occurs due to pathological conditions which may be either fetal or maternal in origin. In addition to low body weight they have abnormal ponderal  index, body disproportion, and low subcutaneous fat deposition. There are two types-symmetrical and asymmetrical. [ 9 ] [ 10 ]  Some conditions are associated with both symmetrical and asymmetrical growth restriction. [ citation needed ]


Asymmetrical IUGR accounts for 70-80% of all IUGR cases. [ 11 ]  In asymmetrical IUGR, there is decreased oxygen or nutrient supply to the fetus during the third trimester of pregnancy due to  placental insufficiency . [ 12 ]  This type of IUGR is sometimes called "head sparing" because brain growth is typically less affected, resulting in a relatively normal head circumference in these children. [ 13 ]  Because of decreased oxygen supply to the fetus, blood is diverted to the vital organs, such as the brain and heart. As a result, blood flow to other organs - including liver, muscle, and fat - is decreased. This causes abdominal circumference in these children to be decreased. [ 13 ]


A lack of  subcutaneous fat  leads to a thin and small body out of proportion with the liver. Normally at birth the brain of the fetus is 3 times the weight of its liver. In IUGR, it becomes 5-6 times. In these cases, the  embryo /fetus has grown normally for the first two  trimesters  but encounters difficulties in the third, sometimes secondary to complications such as pre-eclampsia.     Other symptoms than the disproportion include dry, peeling skin and an overly-thin  umbilical cord . The baby is at increased risk of  hypoxia  and  hypoglycemia . This type of IUGR is most commonly caused by  extrinsic  factors that affect the fetus at later gestational ages. Specific causes include: [ citation needed ]


Symmetrical IUGR is commonly known as  global growth restriction , and indicates that the  fetus  has developed slowly throughout the duration of the pregnancy and was thus affected from a very early stage. The head circumference of such a newborn is in proportion to the rest of the body. Since most  neurons  are developed by the 18th week of gestation, the fetus with symmetrical IUGR is more likely to have permanent neurological  sequelae . Common causes include: [ citation needed ]


IUGR is caused by a variety of factors; these can be fetal, maternal, placental or genetic factors. [ 11 ]


If the cause of IUGR is  extrinsic  to the fetus (parental or uteroplacental), transfer of  oxygen  and nutrients to the fetus is decreased.  This causes a reduction in the fetus' stores of  glycogen  and  lipids .  This often leads to  hypoglycemia  at birth.   Polycythemia  can occur secondary to increased  erythropoietin  production caused by the chronic  hypoxemia .   Hypothermia ,  thrombocytopenia ,  leukopenia ,  hypocalcemia , and  bleeding   in the lungs  are often results of IUGR. [ 5 ]


Infants with IUGR are at increased risk of  perinatal asphyxia  due to  chronic hypoxia , usually associated with  placental insufficiency ,  placental abruption , or a umbilical cord accident. [ 16 ]  This chronic hypoxia also places IUGR infants at elevated risk of  persistent pulmonary hypertension of the newborn , which can impair an infant's  blood oxygenation  and  transition to postnatal circulation . [ 17 ]


If the cause of IUGR is  intrinsic  to the fetus, growth is restricted due to genetic factors or as a sequela of infection. IUGR is associated with a wide range of short- and long-term  neurodevelopmental disorders . [ citation needed ]


In IUGR, there is an increase in  vascular resistance  in the placental circulation, causing an increase in cardiac  afterload . There is also increased  vasoconstriction  of the arteries in the periphery, which occurs in response to chronic  hypoxia  in order to preserve adequate blood flow to the fetus' vital organs. [ 18 ]  This prolonged vasoconstriction leads to remodeling and stiffening of the arteries, which also contributes to the increase in cardiac afterload. Therefore, the fetal heart must work harder to contract during each heartbeat, which leads to an increase in wall stress and cardiac  hypertrophy . [ 19 ]  These changes in the fetal heart lead to increased long-term risk of  hypertension ,  atherosclerosis , cardiovascular disease, and  stroke . [ 19 ]


Normal lung development is interrupted in fetuses with IUGR, which increases their risk for  respiratory compromise  and impaired lung function later in life. Preterm infants with IUGR are more likely to have  bronchopulmonary dysplasia  (BPD), a chronic lung disease that is thought to be associated with prolonged use of mechanical ventilation. [ 19 ]


IUGR is associated with long-term motor deficits and cognitive impairment. [ 19 ]  In order to adapt to the chronic hypoxia associated with placental insufficiency, blood flow is redirected to the brain to try to preserve brain growth and development as much as possible. Even though this is thought to be protective, fetuses with IUGR who have undergone this brain-sparing adaptation have worse neurological outcomes compared with those who have not undergone this adaptation. [ 20 ]


Magnetic resonance imaging  (MRI) can detect changes in volume and structural development of infants with IUGR compared with those whose growth is  appropriate for gestational age  (AGA). But MRI is not easily accessible for all patients. [ 19 ]


White matter  effects – In postpartum studies of infants, it was shown that there was a decrease of the  fractal dimension  of the white matter in IUGR infants at one year corrected age. This was compared to at term and preterm infants at one year adjusted corrected age. [ citation needed ]


Grey matter  effects – Grey matter was also shown to be decreased in infants with IUGR at one year corrected age. [ 21 ]


Children with IUGR are often found to exhibit brain reorganization including neural circuitry. [ 22 ]  Reorganization has been linked to learning and memory differences between children born at term and those born with IUGR. [ 23 ]


Studies have shown that children born with IUGR had lower  IQ . They also exhibit other deficits that point to  frontal lobe  dysfunction. [ citation needed ]


IUGR infants with brain-sparing show accelerated maturation of the  hippocampus  which is responsible for memory. [ 24 ]  This accelerated maturation can often lead to uncharacteristic development that may compromise other networks and lead to memory and learning deficiencies. [ citation needed ]


Mothers whose fetus is diagnosed with intrauterine growth restriction can be managed with several monitoring and delivery methods. It is currently recommended that any fetus that has growth restriction and additional structural abnormalities should be evaluated with  genetic testing . [ 6 ]  In addition to evaluating the fetal  growth velocity , the fetus should primarily be monitored by  ultrasonography  every 3–4 weeks. [ 6 ]  An additional monitoring technique is an  Doppler velocimetry . Doppler velocimetry is useful in monitoring blood flow through the uterine and umbilical arteries, and may indicate signs of  uteroplacental insufficiency . [ 25 ]  This method may also detect blood vessels, specifically the  ductus venosus  and  middle cerebral arteries , which are not developing properly or may not adapt well after birth. [ 25 ]  Monitoring via Doppler velocimetry has been shown to decrease the risk of morbidity and mortality before and after parturition among IUGR patients. [ 26 ]  Standard fetal surveillance via nonstress tests and/or biophysical profile scoring is also recommended. [ 25 ] [ 6 ]   Bed rest  has not been found to improve outcomes and is not typically recommended. [ 27 ]  There is currently a lack of evidence supporting any dietary or supplemental changes that may prevent the development of IUGR. [ 6 ]


The optimal timing of delivery for a fetus with IUGR is unknown. However, the timing of  delivery is currently based on the cause of IUGR [ 6 ]  and parameters collected from the umbilical artery doppler. Some of these include: pulsatility index, resistance index, and end-diastolic velocities, which are measurements of the fetal circulation. [ 26 ]  Fetuses with an anticipated delivery before 34 weeks gestation are recommended to receive corticosteroids to facilitate fetal maturation. [ 6 ] [ 28 ]  Anticipated births before 32 weeks should receive magnesium sulfate to protect development of the fetal brain. [ 29 ]


After correcting for several factors such as low gestational parental weight, it is estimated that only around 3% of pregnancies are affected by true IUGR. 20% of  stillborn  infants exhibit IUGR. Perinatal  mortality rates  are 4-8 times higher for infants with IUGR, and  morbidity  is present in 50% of surviving infants. [ 30 ]  Common causes of mortality in fetuses/infants with IUGR include:  severe placental insufficiency  and chronic hypoxia,  congenital malformations ,  congenital infections ,  placental abruption , cord accidents,  cord prolapse ,  placental infarcts , and  severe perinatal depression . [ 5 ]


IUGR is more common in preterm infants than in full term (37–40 weeks gestation) infants, and its frequency decreases with increasing gestational age. Relative to premature infants who do not exhibit IUGR, premature infants with IUGR are more likely to have adverse neonatal outcomes, including  respiratory distress syndrome ,  intraventricular hemorrhage , and  necrotizing enterocolitis . This association with prematurity suggests utility of screening for IUGR as a potential risk factor for preterm labor. [ 31 ]


Feeding intolerance,  hypothermia ,  hypoglycemia , and  hyperglycemia  are all common in infants in the postnatal period, indicating the need to closely manage these patients' temperature and nutrition. [ 32 ]  Furthermore, rapid metabolic and physiologic changes in the first few days after birth can yield susceptibility to  hypocalcemia ,  polycythemia , immunologic compromise, and  renal dysfunction . [ 33 ] [ 34 ]


According to the theory of  thrifty phenotype , intrauterine growth restriction triggers  epigenetic  responses in the fetus that are otherwise activated in times of chronic food shortage. If the offspring actually develops in an environment where food is readily accessible, it may be more prone to metabolic disorders, such as  obesity  and  type II diabetes . [ 35 ]


Infants with IUGR may continue to show signs of abnormal growth throughout childhood. Infants with asymmetric IUGR (head-sparing) typically have more robust  catch-up postnatal growth , as compared with infants with symmetric IUGR, who may remain small throughout life. The majority of  catch-up growth  occurs in the first 6 months of life, but can continue throughout the first two years. Approximately 10% of infants who are small for gestational age due to IUGR will still have short stature in late childhood. [ 36 ]


Infants with IUGR are also at elevated risk for neurodevelopmental abnormalities, including motor delay and  cognitive impairments . Low  IQ  in adulthood may occur in up to one third of infants born small for gestational age due to IUGR. Infants who fail to display adequate catch-up growth in the first few years of life may exhibit worse outcomes. [ 37 ] [ 38 ]


Catch-up growth can alter fat distribution in children diagnosed with IUGR as infants and increase risk of  metabolic syndrome . [ 39 ]  Infants with IUGR may be susceptible to long-term dysfunction of several endocrine processes, including  growth hormone signaling , the  hypothalamic-pituitary-adrenal axis , and  puberty . [ 40 ]   Renal dysfunction , disrupted lung development, and  impaired bone metabolism  are also associated with IUGR. [ 41 ]


In sheep, intrauterine growth restriction can be caused by heat stress in early to mid pregnancy.  The effect is attributed to reduced placental development causing reduced fetal growth. [ 42 ] [ 43 ] [ 44 ]   Hormonal effects appear implicated in the reduced placental development. [ 44 ]  Although early reduction of placental development is not accompanied by concurrent reduction of fetal growth; [ 42 ]  it tends to limit fetal growth later in gestation.  Normally, ovine placental mass increases until about day 70 of gestation, [ 45 ]   but high demand on the placenta for fetal growth occurs later.  (For example, research results suggest that a normal average singleton Suffolk x Targhee sheep fetus has a mass of about 0.15 kg at day 70, and growth rates of about 31 g/day at day 80, 129 g/day at day 120 and 199 g/day at day 140 of gestation, reaching a mass of about 6.21 kg at day 140, a few days before parturition. [ 46 ] )


In adolescent ewes (i.e. ewe hoggets), overfeeding during pregnancy can also cause intrauterine growth restriction, by altering nutrient partitioning between dam and conceptus. [ 47 ] [ 48 ]   Fetal growth restriction in adolescent ewes overnourished during early to mid pregnancy is not avoided by switching to lower nutrient intake after day 90 of gestation; whereas such switching at day 50 does result in greater placental growth and enhanced pregnancy outcome. [ 48 ]   Practical implications include the importance of estimating a threshold for "overnutrition" in management of pregnant ewe hoggets.  In a study of Romney and Coopworth ewe hoggets bred to Perendale rams, feeding to approximate a conceptus-free live mass gain of 0.15 kg/day (i.e. in addition to conceptus mass), commencing 13 days after the midpoint of a synchronized breeding period, yielded no reduction in lamb birth mass, where compared with feeding treatments yielding conceptus-free live mass gains of about 0 and 0.075 kg/day. [ 49 ]
In both of the above models of IUGR in sheep, the absolute magnitude of uterine blood flow is reduced. [ 48 ]   Evidence of substantial reduction of placental glucose transport capacity has been observed in pregnant ewes that had been heat-stressed during placental development. [ 50 ] [ 51 ]


Linea nigra  (Latin for "black line"), colloquially known as the  pregnancy line , manifests as a linear area of  heightened pigmentation  frequently observed on the abdominal region during  pregnancy . [ 1 ]  Typically spanning approximately one centimeter (0.4 in) in width, this brownish streak extends vertically along the midline of the  abdomen , spanning from the  pubis  to the  umbilicus . Variably, it may traverse from the pubis to the upper abdominal region. [ 2 ]


For pregnant women, the emergence of linea nigra is attributed to an increased production of  melanocyte-stimulating hormone  by the  placenta . [ 3 ]  This physiological phenomenon is concomitant with the occurrence of  melasma  and darkened nipples. Individuals with lighter skin pigmentation tend to exhibit this phenomenon less frequently in comparison to those possessing darker pigmentation. [ 4 ]  It is typical for the linea nigra to fade and dissipate within several months following childbirth.


Although predominantly associated with pregnancy, it can manifest in people of either sex and all ages. Beyond the gestational context, its prevalence is found to be uniformly elevated in either sex during the ages of 11 to 15. This is potentially attributable to hormonal fluctuations characteristic of  puberty . After age 15, the prevalence of the linea nigra declines. Particularly in postpubescent people, it often serves as an indicator of elevated benign  estrogens . The prevalence of this phenomenon drops below 10% following the age of 30. Furthermore, its appearance may ensue after rapid weight gain over a short interval. It could also rarely serve as an indicator of underlying  hormonal imbalances ,  genetic disorders ,  malignancy ,  inflammation , or even  fungal infections . [ 5 ]


Media related to  Linea nigra  at Wikimedia Commons


A  luteoma  is a tumor that occurs in the  ovaries  during pregnancy.
It is associated with an increase of sex  hormones , primarily  progesterone  and  testosterone . [ 1 ] [ 2 ]  The size of the tumor can range from 1 to 25 cm in diameter, but is usually 6 to 10 cm in diameter [ 3 ]  and can grow throughout the duration of the pregnancy. [ 4 ]  However, luteomas are  benign  and resolve themselves after delivery. This type of tumor is rare with only about 200 documented cases; many of these cases were detected accidentally, so the actual rate of occurrence may be higher. The most obvious symptom of a luteoma is  masculinization  of the mother and the possible masculinization of the  fetus . [ 1 ] [ 5 ]  This occurs because of the release of testosterone by the luteoma. Testosterone is a sex hormone most abundant in men although small amounts are naturally present in women. Testosterone is responsible for the male characteristics such as deepening of the voice, growth of dark hair, and acne. [ 6 ]  While not life-threatening, the development of male characteristics associated with luteomas can cause visible changes in the mother and can have drastic effects on the formation of the fetus. Luteomas can cause the fetus to be born with an  ambiguous sex , which, depending on how the parents prefer to raise the infant, may result in the parents choosing a sex for the fetus.


Luteomas can be associated with  disorders of sex development  (formerly known as  pseudohermaphroditism ). [ 7 ]


Luteoma is frequently asymptomatic; only 36% of women actually show signs of masculinization. [ 3 ]  These signs include acne, the  growth of dark hair  (especially on the face), deepening of the voice,  temporal balding , and  clitoromegaly . [ 1 ] [ 8 ]  An increase in testosterone levels in the mother does not necessarily mean masculinization will occur. During a normal pregnancy, the testosterone level will increase slightly in the first and second  trimester , but doubles in the third trimester. The testosterone level also depends on the sex of the fetus; male fetuses cause a bigger increase in testosterone levels than female fetuses. [ 9 ] [ 10 ]


Male fetuses, when carried by a mother who develops male characteristics from a luteoma, are not highly affected by the increase in testosterone in the mother due to this conditions. However, after birth, the male fetus may have abnormally high levels of testosterone, but this resolves itself. There have not been any ties between luteomas and the male infant producing high amounts of testosterone by itself. [ 3 ]


Out of the 36% of women who show male characteristics from the luteoma, 75% of female fetuses will also show signs of masculinization. [ 3 ]  Female fetuses can have a variety of symptoms ranging from severe, requiring surgery, to mild, which resolves itself after birth. The severity of the symptoms a female fetus undergoes depends on when the exposure occurs and the duration of the exposure. If a female fetus is exposed to increased levels of testosterone in the first 7–12 weeks of the pregnancy,  labioscrotal fusion  and clitoromegaly can occur. These conditions would need correctional surgery if the infant was to be raised female. If testosterone exposure occurs after the first 12 weeks of pregnancy, no fusion will occur but the clitoris could still be enlarged. [ 3 ]  The enlarged clitoris usually corrects itself after birth and the abnormally high testosterone levels will decrease as the body produces its own hormones. [ 3 ]


Several conditions predispose a woman to forming a luteoma during pregnancy.  Polycystic ovary syndrome  (PCOS) is one such condition. [ 5 ]  This syndrome is associated with high hormone levels and the failure of the ovaries to release an egg during the  menstrual cycle , a symptom more often associated with  menopause . The high levels of hormones in polycystic ovary syndrome seem to predispose women to forming a luteoma during pregnancy. A characteristic of luteomas is that they grow better in the presence of high levels of hormones that function in normal growth, sexual development, and reproductive function. PCOS causes an excess of hormones in the body including some of the hormones related to these functions. [ 11 ]  Women who have already had a luteoma during a previous pregnancy have a higher high risk of having another luteoma. In this situation, women can be counseled on the risks of another pregnancy and their alternatives.  Other risk factors associated with luteomas are multiple pregnancies, advanced maternal age, and Afro-Caribbean ethnicity. [ 5 ]


Luteomas are not often detected before delivery. Most luteomas are found during surgery if a  caesarean section  is performed or when some other surgery is performed. Pre-delivery detection is not effective for many reasons. Some tests, that can be performed pre-delivery, measure the amount of testosterone in the blood; however, this is not a very useful detection method since normal pregnancies have increased amounts of testosterone. Another method that would be useful to determine if a fetus is being exposed to testosterone is to test the  placenta  and  umbilical cord  for testosterone. The placenta has a mechanism for converting hormones from the mother into hormones that the fetus needs. If the amount of testosterone in the umbilical cord is higher than normal, the  gene  type of the fetus should be determined to see if the fetus is male or female. If the fetus is female then the high levels of testosterone in the umbilical cord could be an indicator that a luteoma is present. This procedure cannot be safely performed until after the fetus has undergone  differentiation  (when the sex of the fetus becomes apparent). But by this time the damage has already been done. [ 3 ]


No treatments for luteomas are currently available. The luteomas can be detected through  ultrasound  if masculinization is apparent in the mother. [ 8 ]  The fetus can be tested for gene type and if the fetus is female and the umbilical cord tests high for testosterone levels then the risks of masculinization of the fetus can be considered. Interventions cannot be made to change the outcomes, but the potential risks can be analyzed in order to make preparations. After the fetus is delivered the luteoma regresses on its own and only monitoring of the mother is needed after delivery. Depending on the sex of the fetus, exposure time and duration, the parents may need to decide if they will raise the child as male or female. Surgery may be necessary depending on what sex the child is going to be raised. [ 3 ]


Erramatti Mangamma  (born 1 September 1946) is an Indian woman who currently holds the record for having given birth at the highest age. [ 1 ]  At the age of 73, she gave birth to twin girls on 5 September 2019. The record was previously held by Daljinder Kaur Gill, who gave birth to a baby boy at the age of 72. [ 2 ]


Mangamma married Sitarama Rajarao in 1962 in  Andhra Pradesh , but the couple were unable to have children until Mangamma was impregnated using  in-vitro fertilisation . [ 3 ]


The couple are believed to have consulted several doctors for a period before Mangamma got pregnant after consulting a village doctor, Shanakkalaya Umashankar, in November 2018. [ citation needed ]  The couple delivered twin girls for the first time after their marriage in 1962. [ 4 ]  Mangamma delivered her twins on 5 September 2019 after being impregnated through the process of  in-vitro fertilisation  via  C-section  in the city of  Hyderabad , making her the world's oldest mother and the oldest mother to give birth to twins. [ 5 ]


Rajarao, her husband, died from a  heart attack  in 2020 at the age of 84. [ 6 ]


This  Indian  biographical article is a  stub . You can help Wikipedia by  expanding it .


Maternal fetal stress transfer  is a physiological phenomenon in which psycho social stress  experienced by a mother during her  pregnancy  can be transferred to the  fetus .  Psychosocial stress  describes the brain's physiological response to perceived social threat. Because of a link in blood supply between a mother and fetus, it has been found that stress can leave lasting effects on a developing fetus, even before a child is born. According to recent studies, these effects are mainly the result of two particular stress biomarkers circulating in the maternal blood supply:  cortisol  and  catecholamines .


Cortisol  is type of hormone called a  glucocorticoid , which glucose usage in the body and tends to be activated during a fight-or-flight response. Cortisol is produced in the adrenal gland, whose activity is mediated by the hypothalamus and pituitary glands of the brain. Together, the collective signaling of the  hypothalamus ,  pituitary gland , and  adrenal gland  is known as the  hypothalamo-pituitary-adrenal (HPA) axis . During a period of psychosocial stress, cortisol is released, leading to physiological manifestations of stress such as increased maternal blood pressure (MBP) and maternal heart rate (MHR). [ 1 ]


In the case of a pregnant woman, the release of cortisol from the adrenal glands also has an effect on the fetus being carried in the womb. Cortisol is a  steroid hormone , and, like all steroid hormones, the receptors for cortisol are located intracellularly. In other words, cortisol does not need an extracellular receptor in order to enter the nucleus of cells and affect their gene expression. Because of this feature of steroid hormones, cortisol diffuses directly across the  placenta , the barrier that separates the fetus from the mother. Luckily, the fetus has a protective mechanism against the inundation of cortisol from a stressed mother. There is an enzyme in the placenta called 11beta-hydroxysteroid dehydrogenase type 2 that is capable of inactivating the vast majority of the cortisol passing through the placental barrier to the fetus. [ 2 ]


In cases of very high levels of maternal cortisol, this placental enzyme's expression and activity are greatly reduced, thus buffering the fetus less from the mother's high cortisol levels. There are detrimental effects to this loss of placental enzymatic activity. One such effect is a change in the set point for the HPA axis. [ 1 ]  Myriad studies in animal models indicate that, if fetal cortisol levels are high, then the HPA axis will be more active postnatally. [ 3 ]


High levels of fetal cortisol induce higher CRH expression in the paraventricular nucleus of the hypothalamus (PVN) and the central nucleus of the amygdala. [ 3 ]  In other words, excessive cortisol crossing the placental barrier causes the hypothalamus and amygdala to increase transcription of CRH, which in turn stimulates HPA axis activity early in postnatal life. With such an overactive HPA axis, glucocorticoid receptor expression in the brain increases, [ 3 ]  making it so that the release of minimal levels of cortisol elicit a substantial response at developing synapses. It is speculated that the HPA axis will more rapidly develop its neural circuitry as a result.


During the pregnancy, a foetus’ brain is extremely malleable as it is in its prime developmental phase. The parts of the brain which are most susceptible to extraneous influences are those responsible for the stress response: the  hypothalamus  and the  pituitary gland . This is due to the fact that the stress response in humans forms very early in our foetal stage, therefore is vulnerable to the mother's mental, physical and emotional state during the gestational period. [ 4 ]


If the mother herself experiences unusually high levels of stress, her body would respond by increasing cortisol levels to an abnormal standing. These hormones would then be passed from the mother's bloodstream into the foetus’. [ 5 ]   The reason that this phenomenon only occurs when the mother is experiencing an excessive amount of stress, and does not occur from the usual, everyday stress that many individuals experience, is due to one protective mechanism that takes place in the  placenta . [ 6 ]


This mechanism can be understood by first comparing cortisol concentrations in mother and foetus.


Cortisol concentrations in the mother are five to ten times higher than the concentration in the foetus. This ratio of maternal : foetus cortisol concentration is maintained by an enzyme in the placenta which alters the cortisol molecule into an inactive  metabolite  (11-keto products), called Placental  11 β-hydroxysteroid-dehydrogenase . The problem lies in the multiplying factor arising from this ratio, i.e., if maternal cortisol levels rise by 10-20% it could cause foetal cortisol levels to double, which is what occurs when the mother experiences psychological distress. [ 6 ]   Additionally, persistent antenatal stress experienced toward the end of the gestation period is shown to inflict severe and permanent damage on the foetus’ physiological development, potentially leading to early growth retardation, aka  intrauterine growth restriction ,  preterm labour  and delayed motor development in infancy. [ 7 ] [ 8 ]


Studying the foetal stress response in vivo is not commonly done due to various ethical considerations, but the few studies which have managed to conduct research into this phenomenon during a human pregnancy have reached similar conclusions. This is that maternal-foetal stress transfer occurs through the mechanism of cortisol moving from mother to baby through the placenta. [ 5 ]  This means that a mother's stress levels become her child's stress levels as she passes down her own over-sensitive stress response, through non-genetic means.


This biological phenomena is problematic due to the impact that an increased level of cortisol has on the foetal HPA axis. The major source of a cortisol increase are stimuli which provoke consistently high levels of psychosocial stress, but another source of high cortisol concentrations that is often overlooked is the ingestion of  alcohol . It is already well known that women who drink alcohol during pregnancy are more likely to give birth to children with physical or neurological defects, but this occurs with large amounts of alcohol intake. Smaller but still significant portions of alcohol intake can trigger a rise in cortisol levels in the mother's bloodstream, hence causing the cortisol levels to rise in the foetus as well, resulting in the same consequences as maternal-foetal stress transfer. [ 9 ]


Obesity later in life is linked to the changes in the HPA-axis activity in the fetus. As mothers experience increased stress, they may begin to participare in risky health behaviors such as poor dietary habits. This increases the chance of obesity in the mother and the fetus. The fetus has an increased chance of obesity as high stress is used to predict the potential environment the fetus lives in. Two specific types of glucocorticoids,  dexamethasone  and  betamethasone , are transferred to the fetus.  CRH  as well, also influences the fetus' health and disease.This exposure, in addition to a higher energy diet, increase the likelihood of obesity later on in life. This is due to glucocorticoids not only regulating stress in the fetus, but also appetite, obesity and metabolism in animals and humans. [ 10 ]


A mother's antenatal stress is correlated with detrimental neurobehavioural outcomes in the child. [ 11 ]  There are a myriad of consequences on a child after birth, such as  psychiatric disorders ,  behavioural abnormalities , dysfunctional emotional regulation and delays in motor production. [ 7 ]


Exposure during important neurodevelopment periods increase risk of metabolic disorders  including  obesity ,  Type 2 diabetes , and a  poor lipid profile . This risk is most present at a later stage of pregnancy and can be seen as early as six months of age. [ 12 ]  The likelihood further increases when children experience high levels of stress. [ 13 ]


The most commonly occurring psychiatric disorders which develop are  attention-deficit / hyperactivity disorder , [ 14 ]   minor depressive  and  neurotic symptoms ,  schizophrenia , a tendency toward  alcoholism / drug-addiction  and  criminal behaviour . [ 8 ]  These psychiatric disorders can, in turn, either lead to or exacerbate behavioural irregularities such as hyperactivity, an unusually low threshold for irritation or frustration, antisocial and inconsiderate behaviour, as well as profuse clinging or crying (especially at a younger age). Furthermore, the feminisation of male behaviour and an increase in timidity has also been observed in children born out of a stressful antenatal environment. [ 15 ]


Biologically speaking, this phenomenon can also cause the  hippocampus , a very important component of the stress response, to be defective and not function as it should. The reason being that the hippocampus is one of the parts of the brain which is seen to be most vulnerable to maternal stress hormones. Some may believe that this physiological consequence of maternal-foetal stress transfer can be said to be the cause of the psychiatric disorders and behavioural abnormalities outlined above, alongside other factors. [ 15 ]


Moreover, an overexposure to cortisol during infancy can lead to the extreme response of desensitisation to cortisol in the child. Desensitisation or the blocking of  cortisol receptors  can occur because of irregularities in the HPA axis, which form in utero due to the passing of cortisol through the placenta from mother to baby. [ 16 ]  The conversion from extremely high to low cortisol levels can be said to be a  defence mechanism  of sorts, as one (unconsciously) experiences withdrawal, avoidance and denial in an effort to disengage with any challenging or discomforting stimuli, sometimes manifesting in  alexithymia . People are often left feeling empty and isolated due to their state of  emotional numbness  and  dissociation . [ 17 ]


The continuity of maternal stress from during, to after, pregnancy is a progression of maternal-foetal stress transfer which is significant in impacting the infant's overall wellbeing. Postnatal maternal stress, such as  postpartum depression , has an enormous impact on the emotion, mental and behavioural growth of a child, hence can aggravate and intensify the impacts of maternal-foetal stress transfer. Roughly 13% of women experience at least one depressive episode during or directly after pregnancy, thus encouraging the increased interest in identifying the effects of antenatal maternal stress on the development of an individual during the foetal and infancy stages of life. [ 4 ]


As stated by  epigenetics  and one of the conclusions of the  nature vs. nurture debate , most behavioural and psychological problems arise due to a combination of biological and environmental/sociocultural factors. Therefore, environmental factors such as parental care and nutritional availability, alongside help given to the child such as  psychotherapy  can aid in the reversal of the impacts of maternal-foetal stress transfer. [ 7 ]


Maternal physiological changes in pregnancy  are the  adaptations  that take place during  pregnancy  that enable the accommodation of the  developing embryo and fetus . These are normal  physiological  adaptations that cause changes in  behavior , the  functioning of the  heart ,  blood vessels , and  blood ,  metabolism  including increases in  blood sugar levels ,  kidney function , posture, and  breathing . During pregnancy numerous  hormones  and  proteins  are secreted that also have a broad range of effects.


Pregnant women experience numerous adjustments in their  endocrine system  that help support the developing fetus. The fetal-placental unit secretes steroid hormones and proteins that alter the function of various maternal  endocrine glands . Sometimes, the changes in certain hormone levels and their effects on their target organs can lead to  gestational diabetes  and  gestational hypertension .


Levels of progesterone and estrogen rise continually throughout pregnancy, suppressing the hypothalamic axis and subsequently the menstrual cycle. The progesterone is first produced by the  corpus luteum  and then by the placenta in the second trimester. Women also experience increased  human chorionic gonadotropin  (β-hCG), which is produced by the placenta. [ 3 ]


The placenta also produces  human placental lactogen  (hPL), which stimulates maternal lipolysis and fatty acid metabolism. As a result, this conserves blood glucose for use by the fetus. It can also decrease maternal tissue sensitivity to insulin, resulting in  gestational diabetes . [ 4 ]


The  pituitary gland  grows by about one-third as a result of hyperplasia of the lactrotrophs in response to the high plasma estrogen. [ 5 ]   Prolactin , which is produced by the lactrotrophs increases progressively throughout pregnancy. Prolactin mediates a change in the structure of the breast  mammary glands  from ductal to lobular-alveolar and stimulates milk production.


Fetal skeletal formation and then later lactation challenges the maternal body to maintain their calcium levels. [ 6 ]  The fetal skeleton requires approximately 30 grams of calcium by the end of pregnancy. [ 5 ]  The mother's body adapts by increasing  parathyroid hormone , leading to an increase in calcium uptake within the gut as well as increased calcium reabsorption by the kidneys. Maternal total serum calcium decreases due to maternal  hypoalbuminemia , but the ionized calcium levels are maintained. [ 5 ]


Total  cortisol  increases to three times of non-pregnant levels by the third trimester. [ 5 ]  The increased estrogen in pregnancy leads to increase corticosteroid-binding globulin production and in response the  adrenal gland  produces more cortisol. [ 5 ]  The net effect is an increase of free cortisol. This contributes to insulin resistance of pregnancy and possibly striae. [ 5 ]  Despite the increase in cortisol, the pregnant mom does not exhibit  Cushing syndrome  or symptoms of high cortisol. One theory is that high progesterone levels act as an antagonist to the cortisol.


The adrenal gland also produces more  aldosterone , leading to an eight-fold increase in aldosterone. [ 5 ]  Women do not show signs of hyperaldosterone, such as hypokalemia, hypernatremia, or high blood pressure.


The adrenal gland also produces more  androgens , such as testosterone, but this is buffered by estrogen's increase in sex-hormone binding globulin (SHBG). [ 5 ]  SHBG binds avidly to testosterone and to a lesser degree DHEA. [ 5 ]


The  thyroid  enlarges and may be more easily felt during the first trimester. The increase in kidney clearance during pregnancy causes more iodide to be excreted and causes relative iodine deficiency and as a result an increase in thyroid size. Estrogen-stimulated increase in thyroid-binding globulin (TBG) leads to an increase in total  thyroxine  (T4), but free thyroxine (T4) and  triiodothyronine  (T3) remain normal. [ 5 ]


A woman's breasts change during pregnancy to prepare them for breastfeeding a baby. Normal changes include:


From about the 16th week of pregnancy the breasts are able to begin to produce milk. It’s not unusual for small amounts of straw-coloured fluid called  colostrum  to leak from the nipples. Breast lumps also sometimes develop during pregnancy but these are generally benign  cysts  or  fibroadenoma  which are not cause for concern. If the nipples begin to leak any blood tinged fluid a woman should consult her doctor. [ 7 ]


Breast development throughout pregnancy may result in significant  Areola  and  Areolar gland  enlargement, erectile nipples, and/or nipple sensitivity. [ 8 ] [ 9 ]


A woman's breasts grow during pregnancy, typically 1 to 2 cup sizes. [ 10 ]  A woman who wore a C cup bra prior to her pregnancy may need to buy an F cup or larger bra while nursing. [ 11 ]  A woman's torso also grows and her bra band size may increase one or two sizes. [ 12 ]  An average of 80% of women wear the wrong bra size, [ 13 ]  and mothers who are preparing to nurse can benefit from a professional bra fitting from a lactation consultant. [ 12 ]  Once the baby is born, after the initial stage of breastfeeding with  colostrum , the mother will experience her breasts filling with milk (sometimes referred to as "the milk coming in"). This can happen up to about 50–73 hours after birth. Once full  lactation  begins, the woman's breasts swell significantly and can feel achy, lumpy and heavy (which is referred to as engorgement). Her breasts may increase in size again by an additional 1 or 2 cup sizes, but individual breast size may vary depending on how much the infant nurses from each breast. [ 12 ]  Changes in breast size during pregnancy may be related to the sex of the infant, as mothers of female infants have greater changes in breast size than mothers of male infants. [ 14 ]


Many people and even medical professionals mistakenly think that  breastfeeding  causes the breasts to  sag  (referred to as  ptosis ). [ 15 ] [ 16 ] [ 17 ]  As a result, some new parents are reluctant to nurse their infants. In February 2009,  Cheryl Cole  told British  Vogue  that she hesitated to breastfeed because of the effect it might have on her breasts. "I want to breastfeed," she said, "but I’ve seen what it can do, so I may have to reconsider." [ 18 ]  In actuality, breastfeeding is not considered to be a major contributor to ptosis of the breasts. In fact, the biggest factors affecting ptosis are cigarette smoking, a woman's  body mass index  (BMI), her  number of pregnancies , her  breast cup size  before pregnancy, and age. [ 19 ] [ 20 ]


Breast size does not determine the amount of milk a woman will produce or whether she will be able to successfully breastfeed her baby. [ 21 ]  Larger breast size pre pregnancy is a sign there are more fatty cells within the breast, which do not affect milk production. A more important indicator is breast changes during the course of pregnancy. If a woman does not experience any nipple or breast changes during pregnancy this is an indication she may have a rare condition such as  breast hypoplasia  which could lead to more difficulty breastfeeding. Women whose breasts are simply smaller but who have experienced some breast changes are likely to have a successful breastfeeding experience.


The heart adapts to the increased cardiac demand that occurs during pregnancy in many ways.


Cardiac output increases throughout early pregnancy, and peaks in the third trimester, usually to 30-50% above baseline. [ 6 ]  Estrogen mediates this rise in cardiac output by increasing the pre-load and stroke volume, mainly via a higher overall blood volume (which increases by 40–50%). [ 22 ]  The heart rate increases, but generally not above 100 beats/ minute. Total systematic vascular resistance decreases by 20% secondary to the vasodilatory effect of progesterone. Overall, the systolic and diastolic blood pressure drops 10–15 mm Hg in the first trimester and then returns to baseline in the second half of pregnancy. [ 6 ]   All of these cardiovascular adaptations can lead to common complaints, such as palpitations, decreased exercise tolerance, and dizziness. [ 6 ]