Pre- and postnatal growth and the neonate

Prenatal Stages

Development of a human from fertilization to delivery at ‘full term’ averages 266 postfertilization days, or 9.5 lunar months (28 day units). It has long been customary to compute the length of a pregnancy, whether in a normal birth or an abortion, from the first day of the last menstrual period of the mother but, as ovulation usually occurs near the fourteenth day of a menstrual cycle, this ‘menstrual age’ is an overestimate of developmental age of about 2 weeks. Estimated in this manner, pregnancy averages 280 days from the last menstrual period or 10 lunar months (40 weeks).

The development of a human from fertilization to birth is divided into two periods: embryonic and fetal. The absolute size of an embryo or fetus does not afford a reliable indication of either its chronological age or the stage of its structural organization, even though graphs based on large numbers of observations have been constructed to provide averages. All such data suffer from the difficulty of timing the moment of conception in humans; in vitro fertilization techniques now accurately time the start of embryonic life ( Ch. 8 ).

The embryonic period was graded or classified into developmental stages or ‘horizons’, on the basis of the internal and external features of approximately 600 sectioned embryos, by , , . These sections formed the basis of the Carnegie system of staging. Streeter’s work and its continuation by , provided, and continues to provide, a sound foundation for embryonic study and a means of comparing stages of human development with those of the animals routinely used for experimental study, namely the chick, mouse and rat.

The postfertilization developmental events in embryonic stages 1–10 are shown in detail in Fig. 8.1 . The stages up to stage 5 are concerned with implantation of the blastocyst. The external appearance of representative stages from stage 6 to stage 23, correlated with the greatest length in millimetres and approximate age in days is shown in Fig. 23.1 . Estimations of embryonic length from fixed histological specimens may be 1–5 mm less than their equivalent in vivo estimates, reflecting the shrinkage caused by the preparative procedures used in embryological studies. , revised some of the ages that had previously been assigned to early Carnegie embryonic stages, pointing out that interembryonic variation might be greater than had been thought and that, consequently, some ages might have been underestimated. They noted that, as a guide, the age of an embryo could reasonably be estimated from the embryonic length within the range 3–30 mm, by adding 29 to the length. Recent use of ultrasound for the examination of human embryos and fetuses in utero has confirmed much of the staging data. However, assigning embryos to a particular stage and the estimated length of days that that stage encompasses remains subject to error. The revisions of age to particular stages given by are followed as closely as possible in what follows.

Obvious external features provide some guidance to the changes occurring within embryos during successive stages. Somite number is related to early embryonic stages; once the number of somites is too great to count with accuracy, the degree of development of the pharyngeal arches is often used. External staging becomes more obvious when the limb buds appear. The upper limb bud is clearly visible at stage 13 (approximately 31–33 days post fertilization) and the acquisition of a distal paddle on the upper limb bud is characteristic by stage 16 (approximately 37–38 days post fertilization). At stage 18 (approximately 42–44 days post fertilization) the lower limb bud has a distal paddle, whereas the upper limb bud has digit rays that are beginning to separate. By stage 23 (approximately 53–58 days post fertilization) the embryo has a head that is almost erect and rounded, and eyelids are beginning to form. The limbs look far more in proportion and fingers and toes are separate. At this stage the external genitalia are well developed, although they may not be sufficiently developed for the accurate determination of the sex.

Stages of embryonic development include all aspects of internal and external morphogenetic change that occur within the embryo during that stage. They are used to convey a snapshot of the status of the development of all body systems within a particular timeframe. Fig. 23.2 gives an overview of the changes in the main body systems over time and also shows the systems and organs at risk at any specific developmental time and the range of anomalies caused by teratogenic insult at a particular time. Historically, the onset of bone marrow formation in the humerus in stage 23 was used by Streeter to indicate the end of the embryonic period and the beginning of the fetal period of prenatal life, after 53–58 days (about 8 weeks) postfertilization. Fig. 23.3 shows embryonic stages 10–23 correlated to postfertilization days of development alongside postmenstrual weeks. The ‘term’ of a pregnancy, i.e. its completion resulting in delivery, is considered clinically normal between 37 and 42 weeks.

In obstetric practice, the period of pregnancy is divided into thirds, termed trimesters. Within this time scale, starting from the last menstrual period, the fetal period commences during the end of the first trimester ( Fig. 23.4 ). Neonates delivered before 37 weeks are called preterm (or premature); those delivered after 42 weeks are post-term. The use of postmenstrual weeks as a timescale for development has now been extended to those fetuses that are delivered before their predicted ‘term’. This terminology removes the ambiguous use of ‘gestation’,’gestational age’ or ‘gestational weeks’, and helpfully standardizes the terminology in studies that continue to document growth postnatally to 64 postmenstrual weeks (the equivalent of 6 postnatal months for a full-term infant born at 40 weeks). Some studies have used the term ‘corrected age’ for follow-up studies on preterm infants, calculated by subtracting the number of weeks born before 40 weeks’ gestation from the chronological age. It is of note that this method is now standardizing 40 weeks as ‘term’ and it is worth considering if all studies of term babies should have their age similarly adjusted if they were born at 38, 39 or 41 weeks.

The period from postmenstrual week 24 and up to 7 days after birth is termed the perinatal period (see Fig. 23.4 ). In the UK fetuses that are delivered and die before postmenstrual week 24 are considered to be miscarriages of pregnancy, although technological advances in neonatal care assist the delivery and support of infants younger than postmenstrual week 24. The neonatal period is considered to extend from birth to 28 days postnatally; the early neonatal period extends from birth to 7 days and the late neonatal period from 7 to 28 days.

Ultrasound staging

The predicted date of full term and delivery is revised after routine ultrasound examination of the fetus. Early ultrasound estimation of fetal age increases the rate of reported preterm delivery (delivery at <37 weeks) compared with estimation based only on the date of the last menstrual period, possibly because delayed ovulation is more frequent than early ovulation ( ).

The difficulty of correlating the appearance of a chorionic sac, embryo or fetus on an ultrasound scan, with age during the first trimester is related to the specificity of reporting the age. An age reported as within a specific postmenstrual week, e.g. week 12, will cover a period of 6 days (12 weeks 0 days up to 12 weeks 6 days, now noted as 12w0d and 12w6d). It is recommended that sonographic estimation of age should be given as postmenstrual weeks and days (i.e. 12 weeks indicates 12w0d) ( ).

First trimester scan

An early ultrasound scan will detect implantation and viability of the embryo once a heartbeat is detected, confirm multiple pregnancy and estimate the date of delivery. Cardiac activity can be identified by the sixth postmenstrual week ( ); note in Fig. 23.2 that this corresponds to approximately stage 10 (28–29 postfertilization days). Crown–rump length measurement, i.e. the greatest distance between the vertex of the skull and the ischial tuberosities, with the fetus in the natural curved position, is the most accurate predictor of the postmenstrual age of the embryo during the first trimester ( ). Greatest length exclusive of the lower limbs is independent of fixed points and thus simpler to measure, and was recommended by ; it is generally taken to be the sitting height in postnatal life. Nuchal translucency is measured between 10 and 14 weeks to diagnose trisomy 21. The development of three-dimensional ultrasound scanning has enabled early detection of many anomalies that were previously diagnosed in the second trimester, including anencephaly, hydrocephalus and encephalocele ( ). Normograms of fetal spine growth constructed for a Taiwan population showed mean spine length increasing linearly between 11 and 14 weeks ( ) and a tendency for spinal extension as early as 11 weeks.

Second trimester scan

Routine scanning at 18–20postmenstrual weeks is used to confirm the delivery date and assess not only the position of the placenta but also the presence of fetal anomalies that would require special intervention following delivery, such as cardiac defects, lung immaturity, renal agenesis, polyhydramnios and defects of the anterior abdominal wall (gastroschisis and exomphalos). Estimations are made of the following: biparietal skull diameter, taken through a plane of section that traverses the third ventricle and thalami; head circumference through a plane that traverses the third ventricle and thalami plus the cavum septi pellucidi anteriorly and the tentorial hiatus posteriorly; abdominal circumference through a plane where the transverse diameter of the liver is greatest, the appearance of the lower ribs is symmetric and the junction of the left and right portal veins is identified; and femoral length, which measures the ossified portions of the diaphysis and metaphyses ( Fig. 23.5 ). Between 15 and 28postmenstrual weeks, the biparietal diameter is the most accurate index of fetal age and the expected date of delivery. Other measurements that may also be taken include the transverse cerebellar diameter and foot length. The amount and type of fetal movement, breathing movements and visceral functions, exemplified by bladder emptying, peristaltic action and colonic echogenicity, are noted. Gender can be identified later in development but this information is not always routinely passed on to parents. Three- and four-dimensional ultrasound scans are now routinely constructed ( Video 23.1 ). For assessment of fetal wellbeing from ultrasound examination see .

Managing fetal anomalies

An outcome of routine ultrasound examination of embryos and fetuses for anomalies may be a change to the perinatal management, i.e. to the time, method and place of delivery of the fetus, or the parents may choose to terminate the pregnancy to minimize concerns about fetal and neonatal suffering and long-term disability. Termination may be chosen for severe, untreatable inherited metabolic disorders (e.g. Tay–Sachs disease), severe chromosomal anomalies (e.g. trisomy 13), lethal bone dysplasias, lethal anomalies such as anencephaly and other extreme neurological defects, and bilateral renal agenesis ( ). Improvements in prenatal screening and diagnosis have led to an overall increase in the prevalence of reported birth defects and overall lower perinatal mortality rates, reflecting increased early terminations of pregnancy ( ).

Magnetic resonance imaging

Advances in prenatal ultrafast magnetic resonance imaging (MRI) now provide further ways to detect fetal anomalies, capturing particularly clear images ( ) ( Fig. 23.6 ). For this reason, MRI is considered a useful adjunct to ultrasound imaging at 20–22postmenstrual weeks because it enables better management planning for known or suspected anomalies ( ).

Fetal surgery

The use of routine ultrasound examination and MRI of fetuses has led to the development of a number of prenatal surgical interventions: e.g. to correct placental or membrane anomalies resulting in twin-to-twin transfusion and the production of amniotic bands ( ); or to offer improved outcomes for meningomyelocele on the basis that the neural tissue may become secondarily damaged by exposure to amniotic fluid and mechanical traumatic injury during gestation ( , , ). Other conditions have also been treated prenatally with limited improvement in mortality. Congenital diaphragmatic hernia has been treated by percutaneous fetoscopic endoluminal tracheal occlusion from 25 to 33postmenstrual weeks to prevent loss of lung fluid and enhance lung growth ( ). Fetal airway patency has also been preserved during birth through perinatal ex utero intrapartum (EXIT) treatment, where a portion of the fetus is delivered through a hysterectomy incision for surgery while the fetus remains attached to the uteroplacental circulation, and the fetus is subsequently completely delivered after the airway procedure is completed ( ).