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

Fetal mortality refers to stillbirths or fetal death. It encompasses any death of a fetus after 20 weeks of gestation or 500 gm. In some definitions of the PNM early fetal mortality (week 20-27 gestation) is not included, and the PNM may only include late fetal death and neonatal death. Fetal death can also be divided into death prior to labor, antenatal (antepartum) death, and death during labor, intranatal (intrapartum) death.

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.

Based on recent (2005) US NCHS data, the rate of multiple births is now approximately 3.4% (4,138,349 total births, of which 139,816 were twins or higher-order multiple births).

The majority of identical twins share a common (monochorionic) placenta, and of these approximately 15% go on to develop TTTS.

By extrapolating the number of expected identical twins (about one-third) from annual multiple births, and the number of twins with monochorionic placentae (about two-thirds), and from these the number thought to develop TTTS (about 15%), there are at least 4,500 TTTS cases per year in the U.S. alone: 139,816 X .33 X .66 X .15 = 4,568 cases of TTTS per year in U.S. (involving more than 9,000 babies.)

Since spontaneous pregnancy losses and terminations that occur prior to 20 weeks go uncounted by the C.D.C., this estimate of TTTS cases may be very conservative.

Although infertility treatments have increased the rate of multiple birth, they have not appreciably diluted the expected incidence of identical twins. Studies show a higher rate of identical twins (up to 20 times with IVF) using these treatments versus spontaneous pregnancy rates.

One Australian study, however, noted an occurrence of only 1 in 4,170 pregnancies or 1 in 58 twin gestations. This distinction could be partly explained by the "hidden mortality" associated with MC multifetal pregnancies—instances lost due to premature rupture of membrane (PROM) or intrauterine fetal demise before a thorough diagnosis of TTTS can be made.

Some doctors recommend complete bed-rest for the mother coupled with massive intakes of protein as a therapy to try to counteract the syndrome. Research completed shows these nutritional supplements do work. Diet supplementation was associated with lower overall incidence of TTTS (20/52 versus 8/51, P = 0.02) and with lower prevalence of TTTS at delivery (18/52 versus 6/51, P = 0.012) when compared with no supplementation. Nutritional intervention also significantly prolonged the time between the diagnosis of TTTS and delivery (9.4 ± 3.7 weeks versus 4.6 ± 6.5 weeks; P = 0.014). The earlier nutritional regimen was introduced, the lesser chance of detecting TTTS ( P = 0.001). Although not statistically significant, dietary intervention was also associated with lower Quintero stage, fewer invasive treatments, and lower twin birth weight discordance. Diet supplementation appears to counter maternal metabolic abnormalities in monochorionic twin pregnancies and improve perinatal outcomes in TTTS when combined with the standard therapeutic options. Nutritional therapy appears to be most effective in mitigating cases that are caught in Quintero Stage I, little effect has been observed in those that are beyond Stage I.

Early neonatal mortality refers to a death of a live-born baby within the first seven days of life, while late neonatal mortality covers the time after 7 days until before 28 days. The sum of these two represents the neonatal mortality. Some definitions of the PNM include only the early neonatal mortality. Neonatal mortality is affected by the quality of in-hospital care for the neonate. Neonatal mortality and postneonatal mortality (covering the remaining 11 months of the first year of life) are reflected in the Infant Mortality Rate.

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.

Transient tachypnea of the newborn occurs in approximately 1 in 100 preterm infants and 3.6-5.7 per 1000 term infants. It is most common in infants born by Cesarian section without a trial of labor after 35 weeks' gestation. Male infants and infants with an umbilical cord prolapse or perinatal asphyxia are at higher risk. Parental risk factors include use of pain control or anesthesia during labor, asthma, and diabetes.

A 2008 bulletin from the World Health Organization estimates that 900,000 total infants die each year from birth asphyxia, making it a leading cause of death for newborns.

In the United States, intrauterine hypoxia and birth asphyxia was listed as the tenth leading cause of neonatal death.

Factors increasing the risk (to either the woman, the fetus/es, or both) of pregnancy complications beyond the normal level of risk may be present in a woman's medical profile either before she becomes pregnant or during the pregnancy. These pre-existing factors may relate to physical and/or mental health, and/or to social issues, or a combination.

Some common risk factors include:

- Age of either parent

- Adolescent parents

- Older parents

- Exposure to environmental toxins in pregnancy

- Exposure to recreational drugs in pregnancy:

- Ethanol during pregnancy can cause fetal alcohol syndrome and fetal alcohol spectrum disorder.

- Tobacco smoking and pregnancy, when combined, causes twice the risk of premature rupture of membranes, placental abruption and placenta previa. Also, it causes 30% higher odds of the baby being born prematurely.

- Prenatal cocaine exposure is associated with, for example, premature birth, birth defects and attention deficit disorder.

- Prenatal methamphetamine exposure can cause premature birth and congenital abnormalities. Other investigations have revealed short-term neonatal outcomes to include small deficits in infant neurobehavioral function and growth restriction when compared to control infants. Also, prenatal methamphetamine use is believed to have long-term effects in terms of brain development, which may last for many years.

- Cannabis in pregnancy is possibly associated with adverse effects on the child later in life.

- Exposure to Pharmaceutical drugs in pregnancy. Anti-depressants, for example, may increase risks of such outcomes as preterm delivery.

- Ionizing radiation

- Risks arising from previous pregnancies:

- Complications experienced during a previous pregnancy are more likely to recur.

- Many previous pregnancies. Women who have had five previous pregnancies face increased risks of very rapid labor and excessive bleeding after delivery.

- Multiple previous fetuses. Women who have had more than one fetus in a previous pregnancy face increased risk of mislocated placenta.

- Multiple pregnancy, that is, having more than one fetus in a single pregnancy.

- Social and socioeconomic factors. Generally speaking, unmarried women and those in lower socioeconomic groups experience an increased level of risk in pregnancy, due at least in part to lack of access to appropriate prenatal care.

- Unintended pregnancy. Unintended pregnancies preclude preconception care and delays prenatal care. They preclude other preventive care, may disrupt life plans and on average have worse health and psychological outcomes for the mother and, if birth occurs, the child.

- Height. Pregnancy in women whose height is less than 1.5 meters (5 feet) correlates with higher incidences of preterm birth and underweight babies. Also, these women are more likely to have a small pelvis, which can result in such complications during childbirth as shoulder dystocia.

- Weight

- Low weight: Women whose pre-pregnancy weight is less than 45.5 kilograms (100 pounds) are more likely to have underweight babies.

- Obese women are more likely to have very large babies, potentially increasing difficulties in childbirth. Obesity also increases the chances of developing gestational diabetes, high blood pressure, preeclampsia, experiencing postterm pregnancy and/or requiring a cesarean delivery.

- Intercurrent disease in pregnancy, that is, a disease and condition not necessarily directly caused by the pregnancy, such as diabetes mellitus in pregnancy, SLE in pregnancy or thyroid disease in pregnancy.

Perinatal asphyxia, neonatal asphyxia or birth asphyxia is the medical condition resulting from deprivation of oxygen to a newborn infant that lasts long enough during the birth process to cause physical harm, usually to the brain. Hypoxic damage can occur to most of the infant's organs (heart, lungs, liver, gut, kidneys), but brain damage is of most concern and perhaps the least likely to quickly or completely heal. In more pronounced cases, an infant will survive, but with damage to the brain manifested as either mental, such as developmental delay or intellectual disability, or physical, such as spasticity.

It results most commonly from a drop in maternal blood pressure or some other substantial interference with blood flow to the infant's brain during delivery. This can occur due to inadequate circulation or perfusion, impaired respiratory effort, or inadequate ventilation. Perinatal asphyxia happens in 2 to 10 per 1000 newborns that are born at term, and more for those that are born prematurely. WHO estimates that 4 million neonatal deaths occur yearly due to birth asphyxia, representing 38% of deaths of children under 5 years of age.

Perinatal asphyxia can be the cause of hypoxic ischemic encephalopathy or intraventricular hemorrhage, especially in preterm births. An infant suffering severe perinatal asphyxia usually has poor color (cyanosis), perfusion, responsiveness, muscle tone, and respiratory effort, as reflected in a low 5 minute Apgar score. Extreme degrees of asphyxia can cause cardiac arrest and death. If resuscitation is successful, the infant is usually transferred to a neonatal intensive care unit.

There has long been a scientific debate over whether newborn infants with asphyxia should be resuscitated with 100% oxygen or normal air. It has been demonstrated that high concentrations of oxygen lead to generation of oxygen free radicals, which have a role in reperfusion injury after asphyxia. Research by Ola Didrik Saugstad and others led to new international guidelines on newborn resuscitation in 2010, recommending the use of normal air instead of 100% oxygen.

There is considerable controversy over the diagnosis of birth asphyxia due to medicolegal reasons. Because of its lack of precision, the term is eschewed in modern obstetrics.

Fetuses with polyhydramnios are at risk for a number of other problems including cord prolapse, placental abruption, premature birth and perinatal death. At delivery the baby should be checked for congenital abnormalities.

Some disorders and conditions can mean that pregnancy is considered high-risk (about 6-8% of pregnancies in the USA) and in extreme cases may be contraindicated. High-risk pregnancies are the main focus of doctors specialising in maternal-fetal medicine.

Serious pre-existing disorders which can reduce a woman's physical ability to survive pregnancy include a range of congenital defects (that is, conditions with which the woman herself was born, for example, those of the heart or , some of which are listed above) and diseases acquired at any time during the woman's life.

Overall, the relative incidence of neonatal encephalopathy is estimated to be between 2 and 9 per 1000 term births. 40% to 60% of affected infants die by 2 years old or have severe disabilities. In 2013 it was estimated to have resulted in 644,000 deaths down from 874,000 deaths in 1990.

There are several pathologic conditions that can predispose a pregnancy to polyhydramnios. These include a maternal history of diabetes mellitus, Rh incompatibility between the fetus and mother, intrauterine infection, and multiple pregnancies.

During the pregnancy, certain clinical signs may suggest polyhydramnios. In the mother, the physician may observe increased abdominal size out of proportion for her weight gain and gestation age, uterine size that outpaces gestational age, shiny skin with stria (seen mostly in severe polyhydramnios), dyspnea, and chest heaviness. When examining the fetus, faint fetal heart sounds are also an important clinical sign of this condition.

HIE is a major predictor of neurodevelopmental disability in term infants. 25 percent have permanent neurological deficits.

It can result in developmental delay or periventricular leukomalacia.

With treatment, maternal mortality is about 1 percent, although complications such as placental abruption, acute renal failure, subcapsular liver hematoma, permanent liver damage, and retinal detachment occur in about 25% of women. Perinatal mortality (stillbirths plus death in infancy) is between 73 and 119 per 1000 babies of woman with HELLP, while up to 40% are small for gestational age. In general, however, factors such as gestational age are more important than the severity of HELLP in determining the outcome in the baby.

Due to the higher incidence of TTN in newborns delivered by caesarean section, it has been postulated that TTN could result from a delayed absorption of fetal lung fluid from the pulmonary lymphatic system. The increased fluid in the lungs leads to increased airway resistance and reduced lung compliance. It is thought this could be from lower levels of circulating catecholamines after a caesarean section, which are believed to be necessary to alter the function of the ENaC channel to absorb excess fluid from the lungs. Pulmonary immaturity has also been proposed as a causative factor. Levels of phosphatidylglycerol (an indicator of lung maturity) were found to be negative in certain newborns

Mild surfactant deficiency has also been suggested as a causative factor.

Its incidence is reported as 0.5-0.9% of all pregnancies, and 10-20% of women with severe pre-eclampsia. HELLP usually occurs in Caucasian women over the age of 25.

Early journal reports of boomerang dysplasia suggested X-linked recessive inheritance, based on observation and family history. It was later discovered, however, that the disorder is actually caused by a genetic mutation fitting an autosomal dominant genetic profile.

Autosomal dominant inheritance indicates that the defective gene responsible for a disorder is located on an autosome, and only one copy of the gene is sufficient to cause the disorder, when inherited from a parent who has the disorder.

Boomerang dysplasia, although an autosomal dominant disorder, is "not" inherited because those afflicted do not live beyond infancy. They cannot pass the gene to the next generation.

Citrullinemia type I (CTLN1), also known as arginosuccinate synthetase deficiency, is a rare disease caused by a deficiency in argininosuccinate synthetase, an enzyme involved in excreting excess nitrogen from the body. There are mild and severe forms of the disease, which is one of the urea cycle disorders.

Lethal congenital contracture syndrome 1 (LCCS1), also called Multiple contracture syndrome, Finnish type, is an autosomal recessive genetic disorder characterized by total immobility of a fetus, detectable at around the 13th week of pregnancy. LCCS1 invariably leads to prenatal death before the 32nd gestational week. LCCS1 is one of 40 Finnish heritage diseases. It was first described in 1985 and since then, approximately 70 cases have been diagnosed.

Fibrochondrogenesis is quite rare. A 1996 study from Spain determined a national minimal prevalence for the disorder at 8 cases out of 1,158,067 live births.

A United Arab Emirates (UAE) University report, from early 2003, evaluated the results of a 5-year study on the occurrence of a broad range of osteochondrodysplasias. Out of 38,048 newborns in Al Ain, over the course of the study period, fibrochondrogenesis was found to be the most common of the recessive forms of osteochondrodysplasia, with a prevalence ratio of 1.05:10,000 births.

While these results represented the most common occurrence within the group studied, they do not dispute the rarity of fibrochondrogenesis. The study also included the high rate of consanguinous marriages as a prevailing factor for these disorders, as well as the extremely low rate of diagnosis-related pregnancy terminations throughout the region.

Mäkelä-Bengs et al. (1997,1998) performed a genome-wide screening and linkage analysis and assigned the LCCS locus to a defined region of 9q34.