Growth and Development - Through the Life Cycle

The rate of human growth and development is higher during gestation than at any time thereafter. If the rate of weight gain achieved in the 9 months of gestation contin-ued after delivery, infants would weigh about 160 pounds at their first birthdays and be

20 feet tall by age 20! Table 4.12 provides an overview of embryonic and fetal growth and development during pregnancy.

Critical Periods of Growth and Development

Fetal growth and develop-ment proceed along geneti-cally determined pathways in which cells are programmed to multiply, differentiate, and establish long-term func-tional levels during set time intervals. Such time intervals are known as critical periods nutrient transfer across the placenta and provides

exam-ples of nutrients transported by each specific mechanism as they are known.

The fetus receives small amounts of water and other nutrients from ingestion of amniotic fluid. By the second half of pregnancy, the fetus is able to swallow and absorb water, minerals, nitrogenous waste products, and other substances in amniotic fluid.²⁷

The Fetus Is Not a Parasite The fetus is not a

“parasite”—it cannot take whatever nutrients it needs from the mother’s body at the mother’s expense. When maternal nutrient intakes fall below optimum levels or adjustment thresholds, fetal growth and development are compromised more than maternal health.¹² In general, nutrients will first be used to support maternal nutrient needs for her health and physiological changes, and next for placental development, before they become available at optimal levels to the fetus. For example:

Underweight women gaining the same amount of

●

weight as normal-weight women tend to deliver smaller infants and to retain more of the weight gained during pregnancy at the expense of fetal growth.¹³

Fetal growth tends to be reduced in pregnant

teen-●

agers who gain height during pregnancy compared to fetal growth in teens who do not grow during pregnancy.²⁸

Vitamin and mineral deficiencies and toxicities

●

in newborns have been observed in women who showed no signs of deficiency or toxicity diseases during pregnancy.¹³

Table 4.11 Mechanisms of nutrient transport across the placenta^13,26

Mechanism Examples of Nutrients

Passive diffusion

(also called simple diffusion)

Nutrients transferred from blood with higher concentration levels to blood with lower concentration levels

Water, some amino acids and glucose, free fatty acids, ketones, vitamins E and K,^a some minerals (sodium, chloride), gases

Facilitated diffusion

Receptors (“carriers”) on cell membranes increase the rate of nutrient transfer

Some glucose, iron, vitamins A and D

Active transport

Energy (from ATP) and cell membrane receptors

Water-soluble vitamins, some minerals (calcium, zinc, iron, potassium) and amino acids

Endocytosis

(also called pinocytosis)

Nutrients and other molecules are engulfed by placenta membrane and released into fetal blood supply

Immunoglobulins, albumin

aVitamin K crosses the placenta slowly and to a limited degree.

Amniotic Fluid The fluid contained in the amniotic sac that surrounds the fetus in the uterus.

Growth Increase in an organism’s size through cell multiplication (hyperplasia) and enlargement of cell size (hypertrophy).

Development Progression of the physical and mental capabilities of an organism through growth and differentiation of organs and tissues, and integration of functions.

Differentiation Cellular acquisition of one or more characteristics or functions different from that of the original cells.

Critical Periods Preprogrammed time periods during embryonic and fetal development when specific cells, organs, and tissues are formed and integrated, or functional levels established. Also called sensitive periods.

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and are most intense during the first 2 months after concep-tion, when a majority of organs and tissues form. On the whole, critical periods represent a “one-way street,” because it is not possible to reverse directions and correct errors in growth or development that occurred during a previous critical period. Consequently, adverse effects of nutritional and other insults occurring during critical periods of growth and development persist throughout life.³⁰

Hyperplasia Critical periods of growth and develop-ment are characterized by hyperplasia, or an increase in cell multiplication. Because every human cell has a spe-cific amount of DNA, periods of hyperplasia can be de-termined by noting times during gestation when the DNA content of specific organs and tissues increases sharply.

The critical period of rapid cell multiplication of the fore-brain, for example, is between 10 and 20 weeks of gesta-tion (Illustragesta-tion 4.7).

The brain is the first organ that develops in humans, and along with the rest of the central nervous system, it is given priority access to energy, nutrient, and oxygen

Table 4.12 Notes on normal embryonic and fetal growth and development^13,29 Day 1 Conception; one cell called the

zygote exists.

Day 2–3 Eight cells have formed (called the morula) and enter the uterine cavity.

Day 6–8 The morula becomes fluid-filled and is renamed the blastocyst. The blastocyst is comprised of 250 cells, and cell differentiation begins.

Day 10 Embryo implants into the uterine wall, where glycogen is accumulating.

Day 12 Embryo is composed of thousands of cells; differentiation well under way.

Utero placental circulation being formed.

Week 4 (21–28 days) ¼ inch long; rudimentary head, trunk, arms; heart “practices” beating;

spinal cord and two major brain lobes present.

Week 5 (28–35 days) Rudimentary kidney, liver, circulatory system, eyes, ears, mouth, hands, arms, and gastrointestinal tract; heart beats 65 times per minute, circulating its own newly formed blood.

Week 7 (49–56 days) ½ inch long, weighs 2–3 g (less than a teaspoon of sugar);

brain sends impulses, gastrointestinal tract produces enzymes, kidney eliminates some waste products, liver produces red blood cells, muscles work. (Approximately 25% of blastocysts and embryos will be lost before 7 weeks.)

Week 9 Embryo now considered a fetus.

Month 3 Weighs 1 oz; primitive egg and sperm cells developed, hard palate fuses, breathes in amniotic fluid.

Month 4 Weighs about 6 oz; placenta diameter is 3 inches.

Month 5 Weighs about 1 lb, 11 inches long; skeleton begins to calcify, hair grows.

Month 6 14 inches long; fat accumulation begins, permanent teeth buds form; lungs, gastrointestinal tract, and kidneys formed but are not fully functional.

Month 7 Gains ½–1 oz per day.

Months 8 and 9 Gains about 1 oz per day;

stores fat, glycogen, iron, folate, B₆ and B₁₂, riboflavin, calcium, magnesium, vitamins A, E, D;

functions of organs continue to develop. Growth rate declines near term. Placenta weighs 500 – 650 g (1–1½ lb) at term.

supplies. Thus, in conditions of low energy, nutrient, and oxygen availability, the needs of the central nervous sys-tem will be met before those of other fetal tissues such as the liver or muscles. The heart and adrenal glands come next after the central nervous system in the hierarchy of targets for preferential nutrient delivery.²⁵

Deficits or excesses in nutrients supplied to the em-bryo and fetus during critical periods of cell multipli-cation can produce lifelong defects in organ and tissue structure and function. The organ or tissue undergoing critical periods of growth at the time of the adverse ex-posure will be affected most.¹⁵ For example, the neu-ral tube develops into the brain and spinal cord during weeks 3 and 4 after conception. If folate supplies are inadequate during this critical period of growth, per-manent defects in brain or spinal cord formation occur, regardless of folate availability at other times. Other tissues—such as the pancreas, which does not undergo rapid cell multiplication until the third trimester of pregnancy—do not appear to be affected by the early shortage of folate.

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cells within the small intestine or neurotransmitters by nerve cells, occur along with increases in cell number and size.¹³ Hypertrophy Periods of hyperplasia-hypertrophy are followed by hypertrophy only. During this phase, cells continue to accumulate protein and lipids, and functional levels continue to grow in sophistication, but cells no longer multiply. Reductions in cell size caused by unfavo-rable nutrient environments or other conditions are asso-ciated with deficits in organ and tissue functions, such as reduced mental capabilities or declines in muscular coor-dination. Such functional changes can often be reduced or reversed later if deficits are corrected.³⁰

Maturation The last phase of growth and development is maturation—the stabilization of cell number and size.

This phase occurs after tissues and organs are fully devel-oped later in life.

Fetal Body Composition

The fetus undergoes marked changes in body composi-tion during pregnancy (Table 4.13). The general trend is toward progressive increases in fat, protein, and mineral content. Some of the most drastic changes take place in the last 5 weeks of pregnancy, when fat and mineral con-tent increase substantially.

Variation in Fetal Growth

Given a healthy mother and fetal access to needed amounts of energy, nutrients, and oxygen and freedom from toxins, fetal genetic growth potential is achieved.³³ However, as evidenced by the relatively high rate of low birth weight in the United States, optimal conditions required for achieve-ment of genetic growth potential often do not exist during pregnancy. Variations in fetal growth and development

0 50

0 4 8 12 16

Age (Months)

20 24 28

DNA (mg)

Normal Marasmus

Illustration 4.8 DNA content of the cerebellum of the human brain in young children dying from non-nutritional causes and from undernutrition.

source: Reprinted from M. Winick, “Malnutrition and Brain Development,”

Some degree of hyperplasia takes place in a number of organs and tissues in the first year or two after birth and during the adolescent growth spurt. Cells of the cen-tral nervous system, for instance, continue to multiply for about two years after birth, but at a much slower pace than early in pregnancy. Skeletal and muscle cells increase in number during the adolescent growth spurt.³¹

In utero and early life changes in DNA content of the brain have been investigated in fetuses, infants, and young children dying from non-nutritional causes and from undernutrition. Illustration 4.8 presents results from one such study that show deficits in DNA content (or cell number) in the brains of children dying of protein-energy malnutrition versus those dying from accidents. Deficits in DNA were apparent a few months after birth, indicating that severe malnutrition early in pregnancy reduced brain cell number in utero.³²

Hyperplasia and Hypertrophy Cell multiplication con-tinues at a lower rate after critical periods of cell multipli-cation and is accompanied by increases in the size of cells.

This phase of growth can be seen in Illustration 4.7, where it begins around 20 weeks in the forebrain when the rate of increase in DNA content slows. Cell size increases mainly due to an accumulation of protein and lipids inside of cells.

Consequently, increases in cell size can be determined by measuring the protein or lipid content of cells. Specialized functions of cells, such as production of digestive enzymes by

10 20

Weeks

30 Birth

Log DNA-P (mmol)

Forebrain

Illustration 4.7 The critical period of cell multiplication of the forebrain. Growth in cell numbers is indicated by increases in DNA content of a given amount of tissue.

source: From J. Dobbing and J. Sands, “Quantitative Growth and Development of Human Brain,” in Archives of Disease of Children, 48(10):757–767. © 1973 BMJ Publishing Group. Reprinted with permission.

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dSGA. If weight, length, and head cir-cumference are less than the 10th per-centile for gestational age, then the newborn is considered pSGA. Approxi-mately two-thirds of SGA newborns in the United States are disproportionately small, and one-third are proportionately small.³³ Illustration 4.9 provides photos of newborns with differing sizes for ges-tational age.

dSGA Infants who are dispropor-tionately small for gestational age look skinny, wasted, and wrinkly. They tend to have small abdominal circumfer-ences, reflecting a lack of glycogen

are not generally due to genetic causes but rather to en-vironmental factors such as energy, nutrient, and oxygen availability, and to conditions that interfere with geneti-cally programmed growth and development. Insulin-like growth factor-1 (IGF-1) is the primary growth stimulator of the fetus. It promotes uptake of nutrients by the fetus and inhibits fetal tissue breakdown. Levels of IGF-1 are sensitive to maternal nutrition; its levels are decreased by undernutrition. Low levels of IGF-1 decrease muscle and skeletal mass and produce asymmetrical growth.²⁵ Fac-tors such as prepregnancy underweight and shortness, low weight gain during pregnancy, poor dietary intakes, smoking, drug abuse, and certain clinical complications of pregnancy are associated with reduced fetal growth.³⁴

Risk of illness and death varies substantially with size at birth and is particularly high for newborns experienc-ing intrauterine growth retardation (IUGR).³⁵ For a por-tion of newborns, smallness at birth is normal and may reflect familial genetic traits. Because IUGR is complicated to determine, it is usually approximated by assessment of size for gestational age using a reference standard (Table 4.14). Infants are generally considered likely to have expe-rienced intrauterine growth retardation if their weight for gestational age or length is low. Newborns whose weight is less than the 10th percen-tile for gestational age are considered small for ges-tational age, or SGA. This determination is further cat-egorized into disproportion-ately small for gestational age (dSGA) and proportion-ately small for gestational age (pSGA). Newborns who weigh less than the 10th per-centile of weight for gesta-tional age but have normal length and head circumfer-ence for age are considered Table 4.13 Estimated changes in body composition of the fetus

by time in pregnancy^{13, 36}

Component 10 Weeks 20 Weeks 30 Weeks 40 Weeks

Body weight, g 10 300 1667 3450

Water, g ,9 263 1364 700

Protein, g ,1 22 134 446

Fat, g ,1 26 66 525

Sodium, meq ,1 32 136 243

Potassium, meq ,1 12 75 170

Calcium, g ,1 1 10 28

Magnesium, mg ,1 5 31 76

Iron, mg ,1 17 104 278

Zinc, mg ,1 6 26 53

Small for Gestational Age (SGA) Newborn weight is #10th percentile for gestational age. Also called small for date (SFD).

Disproportionately Small for Gestational Age (dSGA) Newborn weight is #10th percentile of weight for gestational age; length and head circumference are normal. Also called asymmetrical SGA.

Proportionately Small for Gestational Age (pSGA) Newborn weight, length, and head circumference are

#10th percentile for gestational age. Also called symmetrical SGA.

Illustration 4.9 The newborn on the top is dispropor-tionately small for gestational age, the middle newborn is proportionately small for gestational age, and the newborn on the bottom is large for gestational age.

Publiphoto/Photo Researchers, Inc.AP Photo/Vadim Ghirda, PoolAP Photo/Eleoi Correa, Agencia Estado

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experienced long-term malnutrition in utero, due to factors such as pre-pregnancy underweight, consistently low rates of maternal weight gain in pregnancy and the corresponding inadequate dietary intake, or chronic exposure to alcohol.¹³

Because nutritional insults ex-isted during critical periods of growth early in pregnancy, pSGA infants gen-erally have a reduced number of cells in organs and tissues. These babies tend to exhibit fewer health problems at birth than do dSGA infants, but catch-up growth is poorer, even with nutritional rehabilitation. On aver-age, pSGA infants remain shorter and lighter and have smaller head circum-ferences throughout life than do in-fants born appropriate for gestational age (AGA) or large for gestational age (LGA).³⁷

The goal of nutritional reha-bilitation for pSGA infants should be catch-up in weight and length, and not just weight. This goal appears to be eas-ier to reach if pSGA infants are breast-fed. Excessive weight gain by pSGA infants appears to increase the risk of obesity and insulin- resistance-related disorders, such as hypertension and type 2 diabetes, later in life.³⁸

LGA Newborns with weights greater than the 90th percentile for gestational age are considered to be large for gestational age. About 1–2% of U.S. newborns are LGA. Although it is difficult to predict LGA, it appears to be related to prepregnancy obesity, poorly controlled diabetes in pregnancy, excessive weight gain in pregnancy (over 44 pounds), and possibly other factors.

Except for infants born to women with poorly controlled diabetes during

pregnancy or other health problems, LGA newborns experience far lower illness and death rates than do SGA infants, and they tend to be taller later in life.³⁹ Delivery and postpartum complications in mothers, however, tend to be higher with LGA newborns, and these include increased rates of operative delivery, shoul-der dystocia, and postpar-tum hemorrhage.

stores in the liver, and little body fat. It appears that these infants have experienced in utero malnutrition in the third trimester of pregnancy and that it compromised liver gly-cogen and fat storage. Short-term episodes of malnutri-tion, such as maternal weight loss or low weight gain late in pregnancy that compromise energy, nutrient, or oxygen availability appear to be related to dSGA.³³These infants generally have smaller organ sizes but the normal number of cells in organs and tissues.

Infants who are dSGA are at risk of developing the “hypos” after birth (hypoglycemia, hypocalcemia, hypomagnesi umenia, and hypothermia). If the period of maternal undernutrition was short, dSGA infants tend experience good catch-up growth with nutritional rehabil-itation.²⁵ Unfortunately, disproportionately small infants tend to perform less well aca demically and are at greater risk than other infants for heart disease, hypertension, and type 2 diabetes in the adult years.⁸

pSGA Proportionately SGA newborns look small but well proportioned. It is believed that these infants have

Table 4.14 Percentiles of weight in grams for newborn gestational age

Gestational Age (wk) 5th Pctl 10th Pctl 50th Pctl 90th Pctl 95th Pctl

20 249 275 412 772 912

21 280 314 433 790 957

22 330 376 496 826 1023

23 385 440 582 882 1107

24 435 498 674 977 1223

25 480 558 779 1138 1397

26 529 625 899 1362 1640

27 591 702 1035 1635 1927

28 670 798 1196 1977 2237

29 772 925 1394 2361 2553

30 910 1085 1637 2710 2847

31 1088 1278 1918 2986 3108

32 1294 1495 2203 3200 3338

33 1513 1725 2458 3370 3536

34 1735 1950 2667 3502 3697

35 1950 2159 2831 3596 3812

36 2156 2354 2974 3668 3888

37 2357 2541 3117 3755 3956

38 2543 2714 3263 3867 4027

39 2685 2852 3400 3980 4107

40 2761 2929 3495 4060 4185

41 2777 2948 3527 4094 4217

42 2764 2935 3522 4098 4213

43 2741 2907 3505 4096 4178

44 2724 2885 3491 4096 4122

note: Pctl 5 percentile

source: From Obstetrics and Gynecology, Vol. 87, No. 2, 1996, pp. 163–168, table 2.

Appropriate for Gestational Age (AGA) Weight, length, and head circumference are between the 10th and 90th percentiles for gestational age.

Large for Gestational Age (LGA) Weight for gestational age exceeds the 90th percentile for gestational age. Also defined as birth weight greater than 4500 g ($10 lb) and referred to as excessively sized for gestational age, or macrosomic.

Shoulder Dystocia Blockage or difficulty of delivery due to obstruction of the birth canal by the infant’s shoulders.

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Several studies, but not all, have identified a protective ef-fect of multivitamin supplement use before pregnancy on preterm delivery.^53–55 Additionally, it appears that women who exercise during pregnancy are at lower risk of preterm delivery than are women who do not exercise.⁵⁶

Within the past few years, a number of studies have identified increased levels of cholesterol, triglycerides, or free fatty acids and elevated levels of markers of in-flammation and oxidative stress in the first half of preg-nancy in women delivering preterm.^44,57,59 Higher than average cholesterol levels have been observed as early as 8 weeks of pregnancy in women delivering preterm as.⁴⁴ Elevated levels of these lipids appear to be present early in pregnancy, before major increases in blood lipid lev-els generally occur. This result is raising the question of whether women with high levels of lipids coming into pregnancy are at increased risk of preterm delivery. In-dications of increased inflammatory markers and oxi-dative stress early in pregnancy suggest that chronic inflammation and oxidative stress may be involved in the development of physiological conditions that favor preterm delivery.⁴⁴ Whether diets rich in antioxidant nu-trients and measures that reduce lipid levels and oxida-tive stress decrease the risk for preterm delivery is not currently known.

Although preterm delivery is a major health problem in the United States, its etiology remains unclear, and the search for effective prevention programs continues.⁶⁰ A portion of preterm deliveries appears to be related to geni-tal tract infections, insufficient uterine-placengeni-tal blood flow, placental abruption (bleeding into the uterus), pre-pregnancy underweight, low weight gain in pre-pregnancy, short interpregnancy interval (,6 months), and high lev-els of psychological or social stress. It is also fairly com-mon in women who have previously delivered preterm.⁶⁰ Improvements in prenatal care for women at risk of pre-term delivery—such as close supervision of the pregnancy, inclusion of nutritional counseling, encouragement of adequate weight gain in underweight and normal-weight women, and home visits—appear to decrease the risk of preterm delivery somewhat.⁶¹

The Fetal-Origins

Dalam dokumen Through the Life Cycle (Halaman 125-130)