DES (diethylstilbestrol) is a drug that mimics estrogen, a female hormone. From 1938 until 1971 doctors prescribed this drug to help some pregnant women who had had miscarriages or premature deliveries on the theory that miscarriages and premature births occurred because some pregnant women did not produce enough estrogen naturally to sustain the pregnancy for full term . An estimated 5-10 million pregnant women and the children born during this period were exposed to DES. Currently, DES is known to increase the risk of breast cancer, and cause a variety of birth-related adverse outcomes exposed female offsprings such as spontaneous abortion, second-trimester pregnancy loss, preterm delivery, stillbirth, neonatal death, sub/infertility and cancer of reproductive tissues . DES is an important developmental toxicant which links the fetal basis of adult disease.

Methylmercury and inorganic mercury is excreted in human breast milk and infants are particularly susceptible to toxicity due to this compound. The fetus and infant are especially vulnerable to mercury exposures with special interest in the development of the CNS since it can easily cross across the placental barrier, accumulate within the placenta and fetus as the fetus cannot eliminate mercury and have a negative effect on the fetus even if the mother does not show symptoms. Mercury causes damage to the nervous system resulting from prenatal or early postnatal exposure and is very likely to be permanent.

A study by the Agency for Healthcare Research and Quality (AHRQ) found that of the 3.8 million births that occurred in the United States in 2011, approximately 6.1% (231,900) were diagnosed with low birth weight (<2,500 g). Approximately 49,300 newborns (1.3%) weighed less than 1,500 grams (VLBW). Infants born at low birth weight are at a higher risk for developing neonatal infection.

LBW is closely associated with fetal and Perinatal mortality and Morbidity, inhibited growth and cognitive development, and chronic diseases later in life. At the population level, the proportion of babies with a LBW is an indicator of a multifaceted public-health problem that includes long-term maternal malnutrition, ill health, hard work and poor health care in pregnancy. On an individual basis, LBW is an important predictor of newborn health and survival and is associated with higher risk of infant and childhood mortality.

Low birth weight constitutes as sixty to eighty percent of the infant mortality rate in developing countries. Infant mortality due to low birth weight is usually directly causal, stemming from other medical complications such as preterm birth, poor maternal nutritional status, lack of prenatal care, maternal sickness during pregnancy, and an unhygienic home environment. According to an analysis by University of Oregon, reduced brain volume in children is also tied to low birth-weight.

Genetics plays a role in having a baby born with LGA. Taller, heavier parents tend to have larger babies. Babies born to an obese mother have greatly increased chances of LGA.

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. Hormonal effects appear implicated in the reduced placental development. Although early reduction of placental development is not accompanied by concurrent reduction of fetal growth; it tends to limit fetal growth later in gestation. Normally, ovine placental mass increases until about day 70 of gestation, 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.)

In adolescent ewes (i.e. ewe hoggets), overfeeding during pregnancy can also cause intrauterine growth restriction, by altering nutrient partitioning between dam and conceptus. 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. 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.

In both of the above models of IUGR in sheep, the absolute magnitude of uterine blood flow is reduced. Evidence of substantial reduction of placental glucose transport capacity has been observed in pregnant ewes that had been heat-stressed during placental development.

There are believed to be links with polyhydramnios (excessive amniotic sac fluid). If one has excessive amniotic fluid, microsomia is more likely, since there is no room for the baby to grow. Preterm labor is also highly likely for polyhydramnios.

Not all newborns that are SGA are pathologically growth restricted and, in fact, may be constitutionally small. If small for gestational age babies have been the subject of intrauterine growth restriction (IUGR), formerly known as intrauterine growth retardation, the term SGA associated with IUGR is used.

Intrauterine growth restriction (IUGR) refers to a condition in which a fetus is unable to achieve its genetically determined potential size. This functional definition seeks to identify a population of fetuses at risk for modifiable but otherwise poor outcomes. This definition intentionally excludes fetuses that are small for gestational age (SGA) but are not pathologically small. Infants born SGA with severe short stature (or severe SGA) are defined as having a length less than 2.5 standard deviation scores below the mean.

A related term is low birth weight (LBW), defined as an infant with a birth weight (that is, mass at the time of birth) of less than 2500 g (5 lb 8 oz), regardless of gestational age at the time of birth.

Related definitions include very low birth weight (VLBW) which is less than 1500 g, and extremely low birth weight (ELBW) which is less than 1000 g. Normal Weight at term delivery is 2500 g - 4200 g.

SGA is not a synonym of LBW, VLBW or ELBW.

Example: 35-week gestational age delivery, 2250g weight is appropriate for gestational age but is still LBW. One third of low-birth-weight neonates - infants weighing less than 2500g - are small for gestational age.

There is an 8.1% incidence of low birth weight in developed countries, and 6–30% in developing countries. Much of this can be attributed to the health of the mother during pregnancy. One third of babies born with a low birth weight are also small for gestational age. Infants that are born at low birth weights are at risk of developing neonatal infection.

Both low and high maternal serum Vitamin D (25-OH) are associated with higher incidence SGA in white women, although the correlation does not seem to hold for African American women.

The World Health Organization estimates that malnutrition accounts for 54 percent of child mortality worldwide, about 1 million children. Another estimate also by WHO states that childhood underweight is the cause for about 35% of all deaths of children under the age of five years worldwide.

According to a 2008 review an estimated 178 million children under age 5 are stunted, most of whom live in sub-Saharan Africa. A 2008 review of malnutrition found that about 55 million children are wasted, including 19 million who have severe wasting or severe acute malnutrition.

As underweight children are more vulnerable to almost all infectious diseases, the "indirect" disease burden of malnutrition is estimated to be an order of magnitude higher than the disease burden of the "direct" effects of malnutrition. The combination of direct and indirect deaths from malnutrition caused by unsafe water, sanitation and hygiene (WASH) practices is estimated to lead to 860,000 deaths per year in children under five years of age.

Symmetrical IUGR is less common (20-25%). It 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:

- Early intrauterine infections, such as cytomegalovirus, rubella or toxoplasmosis

- Chromosomal abnormalities

- Anemia

- Maternal substance abuse (prenatal alcohol use can result in Fetal alcohol syndrome)

Risk factors of early neonatal hypocalcemia

- Prematurity

- Perinatal asphyxia

- Diabetes mellitus in the mother

- Maternal hyperparathyroidism

- Intrauterine growth retardation (IUGR)

- Iatrogenic

Risk factors of late neonatal hypocalcemia

- Exogenous phosphate load

- Use of gentamicin

- Gender and ethnic: late neonatal hypocalcemia occurred more often in male infants and Hispanic infants

- Others

A large percentage of children that suffer from PEM also have other co-morbid conditions. The most common co-morbidities are diarrhea (72.2% of a sample of 66 subjects) and malaria (43.3%). However, a variety of other conditions have been observed with PEM, including sepsis, severe anaemia, bronchopneumonia, HIV, tuberculosis, scabies, chronic suppurative otitis media, rickets, and keratomalacia. These co-morbidities tax already malnourished children and may prolong hospital stays initially for PEM and may increase the likelihood of death.

Small for gestational age (SGA) newborns are those who are smaller in size than normal for the gestational age, most commonly defined as a weight below the 10th percentile for the gestational age.

Although protein energy malnutrition is more common in low-income countries, children from higher-income countries are also affected, including children from large urban areas in low socioeconomic neighborhoods. This may also occur in children with chronic diseases, and children who are institutionalized or hospitalized for a different diagnosis. Risk factors include a primary diagnosis of intellectual disability, cystic fibrosis, malignancy, cardiovascular disease, end stage renal disease, oncologic disease, genetic disease, neurological disease, multiple diagnoses, or prolonged hospitalization. In these conditions, the challenging nutritional management may get overlooked and underestimated, resulting in an impairment of the chances for recovery and the worsening of the situation.

PEM is fairly common worldwide in both children and adults and accounts for 6 million deaths annually. In the industrialized world, PEM is predominantly seen in hospitals, is associated with disease, or is often found in the elderly.

Diarrhea and other infections can cause malnutrition through decreased nutrient absorption, decreased intake of food, increased metabolic requirements, and direct nutrient loss. Parasite infections, in particular intestinal worm infections (helminthiasis), can also lead to malnutrition. A leading cause of diarrhea and intestinal worm infections in children in developing countries is lack of sanitation and hygiene. Other diseases that cause chronic intestinal inflammation may lead to malnutrition, such as some cases of untreated celiac disease and inflammatory bowel disease.

Children with chronic diseases like HIV have a higher risk of malnutrition, since their bodies cannot absorb nutrients as well. Diseases such as measles are a major cause of malnutrition in children; thus immunizations present a way to relieve the burden.

GDM poses a risk to mother and child. This risk is largely related to uncontrolled high blood glucose levels and its consequences. The risk increases with higher blood glucose levels. Treatment resulting in better control of these levels can reduce some of the risks of GDM considerably.

The two main risks GDM imposes on the baby are growth abnormalities and chemical imbalances after birth, which may require admission to a neonatal intensive care unit. Infants born to mothers with GDM are at risk of being both large for gestational age (macrosomic) in unmanaged GDM, and small for gestational age and Intrauterine growth retardation in managed GDM. Macrosomia in turn increases the risk of instrumental deliveries (e.g. forceps, ventouse and caesarean section) or problems during vaginal delivery (such as shoulder dystocia). Macrosomia may affect 12% of normal women compared to 20% of women with GDM. However, the evidence for each of these complications is not equally strong; in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study for example, there was an increased risk for babies to be large but not small for gestational age in women with uncontrolled GDM. Research into complications for GDM is difficult because of the many confounding factors (such as obesity). Labelling a woman as having GDM may in itself increase the risk of having an unnecessary caesarean section.

Neonates born from women with consistently high blood sugar levels are also at an increased risk of low blood glucose (hypoglycemia), jaundice, high red blood cell mass (polycythemia) and low blood calcium (hypocalcemia) and magnesium (hypomagnesemia). Untreated GDM also interferes with maturation, causing dysmature babies prone to respiratory distress syndrome due to incomplete lung maturation and impaired surfactant synthesis.

Unlike pre-gestational diabetes, gestational diabetes has not been clearly shown to be an independent risk factor for birth defects. Birth defects usually originate sometime during the first trimester (before the 13th week) of pregnancy, whereas GDM gradually develops and is least pronounced during the first and early second trimester. Studies have shown that the offspring of women with GDM are at a higher risk for congenital malformations. A large case-control study found that gestational diabetes was linked with a limited group of birth defects, and that this association was generally limited to women with a higher body mass index (≥ 25 kg/m²). It is difficult to make sure that this is not partially due to the inclusion of women with pre-existent type 2 diabetes who were not diagnosed before pregnancy.

Because of conflicting studies, it is unclear at the moment whether women with GDM have a higher risk of preeclampsia. In the HAPO study, the risk of preeclampsia was between 13% and 37% higher, although not all possible confounding factors were corrected.

Gestational diabetes affects 3–10% of pregnancies, depending on the population studied.

Neonatal hypocalcemia is an abnormal clinical and laboratory hypocalcemia condition that is frequently observed in infants.[1]

Healthy term infants go through a physiological nadir of serum calcium levels at 7.5 - 8.5 mg/dL by day 2 of life. Hypocalcemia is a low blood calcium level. A total serum calcium of less than 8 mg/dL (2mmol/L) or ionized calcium less than 1.2 mmol/L in term neonates is defined as hypocalcemia. In preterm infants, it is defined as less than 7mg/dL (1.75 mmol/L) total serum calcium or less than 4mg/dL (1 mmol/L) ionized calcium. [2]

Both early onset hypocalcemia (presents within 72h of birth) and late onset hypocalcemia (presents in 3-7 days after birth) require calcium supplementation treatment.

Tricho-hepato-enteric syndrome is estimated to affect 1 in 300,000 to 400,000 live births in Western Europe. This syndrome was first reported in 1982 with a report on 2 siblings, and as of 2008 there were around 25 published cases in medical journals. There seem to be no racial differences in its occurrence. It might be more common, as many genetic diseases, in areas with high levels of consanguinity.

Elevated levels of the alkaline phosphatase enzyme are reported with those who have obesity. A study reported there were higher serum levels of alkaline phosphatase in obese than in the non obese. With elevated alkaline phosphatase levels there is an increase in disproportionate intracellular fat depots and thereby releasing itself into the bloodstream. The relationship between alkaline phosphatase and obesity is still being tested.

As there is no known cure, few people with progeria exceed 13 years of age. At least 90% of patients die from complications of atherosclerosis, such as heart attack or stroke.

Mental development is not adversely affected; in fact, intelligence tends to be average to above average. With respect to the features of aging that progeria appears to manifest, the development of symptoms is comparable to aging at a rate eight to ten times faster than normal. With respect to features of aging that progeria does not exhibit, patients show no neurodegeneration or cancer predisposition. They also do not develop conditions that are commonly associated with aging, such as cataracts (caused by UV exposure) and osteoarthritis.

Although there may not be any successful treatments for progeria itself, there are treatments for the problems it causes, such as arthritic, respiratory, and cardiovascular problems. Sufferers of progeria have normal reproductive development and there are known cases of women with progeria who had delivered healthy offspring.

Elevated serum levels of alkaline phosphatase has been associated with Chronic Kidney Disease (CKD). Recently, studies have shown that elevated levels may predict mortality independent of bone metabolism factors and liver function tests in CKD. This distinction is indicated by the markers of inflammations specifically from C-reactive protein (CRP) with elevated levels of alkaline phosphatase. Hence, elevated serum alkaline phosphatase activity may be a marker for inflammation because of its association with elevated levels of CRP.

- Chronic kidney disease

Tricho-hepato-enteric syndrome (THE), also known as syndromic or phenotypic diarrhea, is an extremely rare congenital bowel disorder which manifests itself as intractable diarrhea in infants with intrauterine growth retardation, hair and facial abnormalities. Many also have liver disease and abnormalities of the immune system. The associated malabsorption leads to malnutrition and failure to thrive.

It is thought to be a genetic disorder with an autosomal recessive inheritance pattern, although responsible genes have not been found and the exact cause remains unknown. Prognosis is poor; many patients die before the age of 5 (mainly from infections or cirrhosis), although most patients nowadays survive with intravenous feeding (parenteral nutrition).

The cause is not known but is often associated with some:

- fetal chromosomal anomalies

- intra uterine infections

- drugs; PG inhibitors, ACE inhibitors

- renal agenesis or obstruction of the urinary tract of the fetus preventing micturition such as posterior urethral valves in males

- intrauterine growth restriction (IUGR) associated with placental insufficiency

- "amnion nodosum"; failure of secretion by the cells of the amnion covering the placenta

- postmaturity (dysmaturity)

Risk factors for developing antiphospholipid syndrome include:

- Primary APS

- genetic marker HLA-DR7

- Secondary APS

- SLE or other autoimmune disorders

- Genetic markers: HLA-B8, HLA-DR2, HLA-DR3

- Race: Blacks, Hispanics, Asians, and Native Americans

There is an additional elevated risk of adrenal gland bleeds leading to Waterhouse–Friderichsen syndrome (Neisseria meningitidis caused primary adrenal insufficiency). This will require adrenal steroid replacement treatment for life.