Indications for first trimester ultrasound are listed in Table 4-1. When used for gestational age assessment, first trimester crown–rump measurement is the most accurate means for ultrasound dating of pregnancy (2). Ultrasonography may be considered to confirm menstrual dates if there is a gestational age agreement within 1 week by crown–rump measurements (2) (Fig. 4-1). Maximum embryo length at 6 to 10 weeks of gestation and crown–rump length, which represents the maximum length of the fetus from the top of the head to the rump region, are the most accurate at determining gestational age (3).

If a multiple gestation is detected, the first trimester is the optimal period to determine chorionicity (number of placentas) and amnionicity (number of amniotic sacs). Accurate determination of this is critical for the determination of fetal surveillance and timing of delivery in a twin gestation.

There are many indications for second and third trimester ultrasound (Table 4-2). When used for assessment of gestational age, ultrasound may be considered confirmatory of menstrual dates if there is a gestational age agreement within 10 days by an average of multiple fetal biometric measurements obtained in the second trimester (up to 20 weeks of gestation) (6). Determination of gestational age by ultrasonographic biometry alone in the first half of pregnancy has been shown to be a more accurate predictor of the delivery date than using menstrual data alone or in combination with ultrasonography (7,8,9). The biparietal diameter (BPD), head circumference, abdominal circumference, and femoral diaphysis length are the parameters used to estimate gestational age and fetal weight to (Figs. 4-4 to 4-6).

In the absence of specific indications, ultrasound examination between 18 and 20 weeks of gestation allows for a reasonable survey of fetal anatomy and an accurate estimation of gestational age. At this gestational age, anatomically complex organs, such as the fetal heart and brain, can be imaged with
sufficient clarity to allow detection of many major malformations at a time when termination of pregnancy may still be an option (2). The essential elements of a standard fetal anatomic survey are listed in Table 4-3.

Preterm birth is defined as delivery prior to 37 weeks of gestation. In the United States, it affects 12% of all births and is the leading cause of neonatal mortality and cerebral palsy. Despite advances in medicine, preterm births have increased by one-third over the last 25 years. The rate was 9.5% in 1981, 10.6% in 1990, 12.7% in 2005, and 12.8% in 2006 (13).
This increase has been attributed to the increased number of late preterm births (between 34 and 36 weeks of gestation) and the increased number of multi-fetal gestations secondary to fertility therapies (13,14,15,16).

Since 1970s, antenatal corticosteroid administration has been one of the most effective and cost-efficient prenatal interventions for preventing perinatal morbidity and mortality related to preterm birth (17). Antenatal corticosteroid therapy leads to improvement in neonatal lung function by enhancing maturational changes in lung architecture and by inducing type II alveolar cells that increase surfactant production (18). Antenatal corticosteroid therapy reduces the incidence of respiratory distress syndrome (RDS), intraventricular hemorrhage, necrotizing enterocolitis, sepsis, and neonatal mortality by approximately 50% (17). Maximum benefit is seen if delivery occurs more than 24 hours and less than 7 days after initiation of therapy. These effects are not limited by infant gender or race (19), however efficacy in multi-fetal gestations is less clear. A course
of antenatal corticosteroids consists of 12 mg betamethasone intramuscularly every 24 hours for two doses or 6 mg dexamethasone intramuscularly every 12 hours for four doses (20,21). The American College of Obstetricians and Gynecologists (ACOG) recommends a single course of corticosteroids be given to all pregnant women between 24 and 34 weeks of gestation who are at risk of preterm delivery within 7 days. A single course of antenatal corticosteroids should be administered to women with preterm premature rupture of membranes (PPROM) before 32 weeks of gestation. The efficacy of antenatal corticosteroid use at 32 to 33 weeks of gestation for PPROM is unclear based on available evidence, but treatment may be beneficial, particularly if pulmonary immaturity is documented (20).

The lower limit of estimated gestational age for corticosteroid administration is approximately 24 weeks since there is a presumed inability of type II alveolar cells to respond at earlier gestational ages (22). Earlier administration might be justifiable only if aggressive perinatal interventions are planned for deliveries at 23 to 24 weeks of gestation. In a retrospective cohort study of neonates born at 23 weeks of gestation between 1998 and 2007, the authors concluded that neonates whose mothers completed a full course of antenatal corticosteroids had an associated 82% reduction in odds of death. Since RDS was uniform throughout their study population and 50% of the neonates exposed to steroids and survived to discharge experienced necrotizing enterocolitis or intraventricular hemorrhage or both, it was postulated that the survival benefit at this early gestational age may primarily be related to the beneficial effects of antenatal corticosteroids in tissues outside of the lung (18,23).

Approximately one-third of the cases of cerebral palsy are associated with early preterm birth. Observational studies in the 1990s found that children born preterm who were exposed prenatally to magnesium sulfate for obstetric indications such as seizure prophylaxis (in preeclampsia) or tocolysis (in threatened preterm birth) had decreased rates of cerebral palsy as compared with children born preterm to women not exposed to magnesium sulfate (24,25,26). Magnesium sulfate is thought to induce its neuroprotective effects by reducing vascular instability, preventing hypoxic damage and mitigating cytokine or excitatory amino acid damage, all of which threaten the vulnerable preterm brain. Subsequently, several large randomized prospective clinical trials were performed to evaluate the utility of magnesium sulfate for fetal and neonatal neuroprotection (27,28,29,30,31).

In the most recent multicenter, placebo-controlled, randomized trial by Rouse et al. that was conducted at 20 participating NICHHD and Maternal Fetal Medicine Unit sites across the United States, 2,241 women at imminent risk for preterm birth between 24 and 32 weeks of gestation were randomly assigned to receive either IV magnesium sulfate or placebo (31). The risks for preterm birth included PPROM (87%), advanced preterm labor (10%), or indicated preterm delivery (3%). Although the composite study endpoint of neonatal death or cerebral palsy at 2 years of age was not found to be different between the magnesium and placebo treatment groups, a significant reduction in moderate or severe cerebral palsy among children whose mothers received magnesium sulfate (1.9% vs. 3.5%; relative risk, 0.55; 95% CI, 0.32 to 0.95) was noted. In contrast to previous trials, retreatment with magnesium sulfate was permitted in this study.

The Cochrane review (32) on the use of magnesium sulfate for neuroprotection of the fetus in women at risk for preterm birth included five randomized, placebo-controlled trials involving 6,145 babies and concluded that “the neuroprotective role for antenatal magnesium sulfate therapy given to women at risk of preterm birth for the preterm fetus is now established.” There was a reduction in cerebral palsy for all the five studies (5,357 infants) that recruited women at less than 34 weeks gestation (RR 0.69, 95% CI 0.54 to 0.88). The number of women needed-to-be-treated to benefit one baby by avoiding cerebral palsy was 63. In addition, secondary analyses of some of the studies demonstrated an improvement in gross motor function (33).

Since the available evidence suggests that magnesium sulfate given before anticipated early preterm birth (up to 34 weeks of gestation) reduces the risk of cerebral palsy in surviving infants (34), ACOG recommends that physicians electing to use magnesium sulfate for fetal neuroprotection should develop specific guidelines regarding inclusion criteria, treatment regimens, management of concurrent tocolysis, and monitoring requirements in accordance with one of the larger trials (29,30,31).

Indications for third trimester ultrasound are listed in Table 4-2. A common use of third trimester ultrasound is assessment of fetal growth and amniotic fluid volume (AFV). Fetal growth is assessed indirectly throughout gestation with use of fundal height measurements during the prenatal care visits. Between 20 and 34 weeks of gestation, the height of the uterine fundus measured in centimeters correlates closely with gestational
age in weeks (35,36,37). Human fetal growth is characterized by sequential patterns of tissue and organ growth, differentiation and maturation. Development is determined by maternal provision of substrate, placental transfer of these substrates, and fetal growth potential governed by the genome (38). The fetus grows at a rate of approximately 5 g/day at 15 weeks of gestation, 15 to 20 g/day at 24 weeks of gestation, and 30 to 35 g/day at 34 weeks of gestation, however there is considerable biological variation in the velocity of fetal growth (39).