The Impact of Maternal Illness on the Neonate
Dimitry Zilberman
Torre Halscott
Helain J. Landy
▪ INTRODUCTION
Chronic and acute maternal illness can have implications for the developing fetus and newborn, some of which may be life long. Because the topic is too broad for adequate coverage in a single chapter, we focus on several important areas pertaining to the effect of maternal illness on the developing fetus and the newborn.
▪ PRETERM DELIVERY
Preterm birth (PTB) is the greatest contributor to overall neonatal morbidity and mortality (1). In 2010, more than 10% of infants were born prematurely worldwide, and the rate in the United States reached almost 12% (1). PTB is a contributing factor for at least half of all neonatal deaths and morbidities, some of which can be life-long, including neurodevelopmental issues, chronic lung disease, increased risk of infection, visual impairment, gastrointestinal and renal dysfunction, poor weight gain, and prolonged hospital stays (1,2). Increasing evidence suggests that PTB portends other long-term concerns, including medical issues such as hypertension and cardiovascular disease, and potentially impacts on family life and health care delivery systems (1,2).
Underlying reasons for PTB are many, varied, and often multifactorial. Causes for PTB can be grouped into spontaneous (preterm labor with intact membranes or following preterm premature rupture of the membranes [PPROM]) and indicated (labor induction or cesarean delivery for maternal or fetal indications) (1,2,3). Several factors have been identified with spontaneous PTB, although the basic cause remains unknown. Efforts to eradicate or reduce PTB have failed. Currently, it is understood that PTB is the final common pathway for multiple pathophysiologic processes that lead to initiation and progression of preterm labor (2). Important risk factors are a prior history of PTB (2) and uterine overdistension, as with multiple pregnancies that have a preterm delivery rate of almost 10 times that of singletons (1). Other important factors include infection (urinary tract infections, sexually transmitted infections, ascending intrauterine infection); inflammation, possibly resulting from cervical insufficiency; genetic propensity; and environmental exposures such as cigarette smoking (1,2). Racial differences exist, and higher PTB rates are noted among African American and Afro-Caribbean women, only partly due to low socioeconomic and educational status (2). Indicated PTB may result from a number of maternal conditions (such as previous uterine scar, preeclampsia or eclampsia) or fetal conditions (such as multiple gestations or fetal growth restriction [FGR]) (4).
The American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal Fetal Medicine have endorsed a new definition of term pregnancy, replacing the label “term” with early term, full term, late term, and postterm (Table 13.1) (5). In addition, ACOG has published recommendations for timing of delivery for a number of maternal and fetal conditions, to aid in decisions where maternal and neonatal risks need to be assessed relative to the risk of an early delivery (Table 13.2) (6).
Screening
Several risk scoring systems that rely predominantly on the previous obstetric history have not reliably identified those women at risk for preterm delivery. Further, optimal screening protocols in low-risk women have not been ascertained (3). Transvaginal ultrasound measurement of cervical length has become an important tool in assessing the risk for PTB (4,7). A short cervical length, generally before 24 to 28 weeks of gestation and usually defined as less than 25 mm, is associated with an increased risk of PTB (5). Combining cervical length measurements with testing for fetal fibronectin (fFN), a biomarker in vaginal secretions, may further stratify a patient’s individual risk (4,8). Studies have been inconsistent, however, and the benefit of testing for fFN lies in its high negative predictive value (96%), thus excluding an elevated risk for PTB (4,8).
Interventions
Many interventions have been proposed to lower the risk of PTB. Activity modification, nutritional supplements, intensive prenatal care, home uterine monitoring, or antibiotic therapy for bacterial vaginosis have not been successful (3,4). The use of progesterone supplementation, however, is a promising treatment that has become standard management to reduce recurrent PTB. In women with a prior PTB, weekly intramuscular administration of 250 mg of 17-alpha hydroxyprogesterone caproate, given from 16 to 36 weeks of gestation, has been shown to reduce the risk of recurrent preterm delivery by about one-third (9). Similar risk reductions for recurrent PTB have been reported using vaginal progesterone, although trials are ongoing (10). In some situations, based on past history or the sonographic finding of a short cervix (<25 mm before 24 weeks of gestation), cerclage placement may be beneficial (3,4).
Once preterm labor and progressive cervical changes occur, significant prolongation of the gestation may not be feasible. However, treatment modalities can be implemented to reduce the neonatal morbidity and mortality associated with prematurity. One major approach is maternal transfer prior to delivery to a site that is equipped to care for preterm infants (3). Another focus has been maternal administration of corticosteroids (betamethasone 12 mg intramuscularly for two doses 24 hours apart or dexamethasone 6 mg intramuscularly for four doses 12 hours apart) between 24 and 34 weeks’ gestation to decrease neonatal morbidity and mortality from respiratory distress, intraventricular hemorrhage, necrotizing enterocolitis, patent ductus arteriosus, and bronchopulmonary dysplasia, as well as lower overall mortality (3). Various tocolytic agents (magnesium sulfate, calcium channel blockers, or nonsteroidal anti-inflammatory agents such as indomethacin) can reduce uterine contractility. Most data demonstrate, at best, a delay in delivery for only up to 48 hours to allow for corticosteroid administration (3,4,11). Recently, it has been shown that maternal administration of magnesium sulfate can have an added benefit in reducing the risk of neonatal neurodevelopmental morbidity, particularly cerebral palsy, associated with PTB (12). In patients with PPROM who do not progress into active preterm labor, broad-spectrum antibiotics can prolong gestation by up to 1 week, allowing for corticosteroid administration, decreasing maternal and neonatal infectious morbidity, and reducing neonatal morbidity from delivery at earlier gestational ages (13).
▪ MODIFIABLE RISK FACTORS
Preconception counseling is focused on identification of modifiable and nonmodifiable risk factors to aim at achieving successful pregnancies and optimizing neonatal outcome. Nonmodifiable risk factors such as maternal age, genetic disease, or mutation carrier status can guide appropriate evaluation of the partner and promote
conversations regarding options such as preimplantation genetic diagnosis or prenatal diagnostic procedures for a future pregnancy.
conversations regarding options such as preimplantation genetic diagnosis or prenatal diagnostic procedures for a future pregnancy.
TABLE 13.1 Current Recommended Definition of Term Pregnancy (5) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
One of the most important modifiable risk factor prior to pregnancy is cigarette smoking. The prevalence of smoking can range from 5% to 35%, depending on the region studied (14). Smoking and secondhand exposure is associated with PTB, PPROM, placental abruption, small for gestational age (SGA) neonates, and sudden infant death syndrome. Adjuvant pharmacotherapy (nicotine replacement therapy and bupropion) can be used during pregnancy to assist in smoking cessation if needed.
TABLE 13.2 Recommendations for Timing of Delivery with Pregnancy Complications (6) | |||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| |||||||||||||||||||||||||||||||||||||||||||||||
The most significant example of the importance of preconception care is pregestational diabetes mellitus (DM), with its associated increased risks of miscarriage and fetal anomalies from hyperglycemia at the time of conception and during the 1st weeks of embryonic development (15). Thyroid disease, phenylketonuria, seizure disorders, hypertension, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), chronic renal disease, cardiovascular disease, thrombophilia, and asthma are other underlying medical issues where preconception counseling may be helpful, especially in discussing the avoidance of agents that may be teratogenic (15).
▪ OBESITY AND EFFECT OF BARIATRIC SURGERY
Two-thirds of women entering pregnancy in the United States are overweight (body mass index [BMI] at least 25 kg/m2), and one-quarter are obese (BMI at least 30 kg/m2). Overweight and obese women experience more infertility and early pregnancy failure, as well as higher risks of maternal complications and birth defects. It is unclear if obesity by itself or the associated comorbidities such as DM and insulin resistance are the cause of these pregnancy-related complications in these women. Obese pregnant women have higher risks for congenital anomalies (neural tube defects [NTDs], spina bifida, and cardiovascular abnormalities), although maternal obesity appears to protect against fetal gastroschisis (16).
During pregnancy, obese women have higher risks for developing gestational diabetes mellitus (GDM) and preeclampsia, as well as indicated PTB, predominantly for maternal or fetal benefit. Some studies also show higher rates of spontaneous PTB (17). Obesity also confers the additional risks associated with increased rates of cesarean delivery (both planned and emergency cases) and delivering a macrosomic infant (over 4,500 g) that can predispose to birth trauma and shoulder dystocia (18). Even in the absence of GDM and hypertensive diseases of pregnancy, obese women have elevated stillbirth risks (18,19).
Optimal pregnancy weight gain has not been well established. Excessive weight gain in overweight women can increase risks of hypertensive disorders, GDM, cesarean delivery, and weight retention postpartum, in addition to affecting the child’s future risk of developing DM, hypertension, and cardiovascular disease (20,21). In 2009, the Institute of Medicine released guidelines on weight gain in pregnancy for all weight classes for singleton and twin gestations (22) (Table 13.3). Prior to conception, a woman’s BMI should ideally be within the normal range (18 to 25 kg/m2).
Bariatric surgery has become an increasingly common method for morbidly obese individuals (BMI 40 to 44.9 kg/m2) to achieve sustainable weight loss. Since 40% of these procedures are performed in women of reproductive age, pregnancies are common. Delaying pregnancy after bariatric surgery for at least 12 to 24 months is advised to correct surgical issues, manage nutritional deficiencies, allow for optimal weight loss, and maximize pregnancy outcome (23). Timing of pregnancy should be individualized based on preprocedure weight, comorbidities, and the type
of procedure (restrictive such as gastric banding or malabsorption such as Roux-en-Y gastric bypass). Bariatric surgery, particularly malabsorptive procedures, has been associated with a two-fold increase in SGA infants although, in spite of nutritional deficiencies, the risk of congenital anomalies does not differ from the general population (23).
of procedure (restrictive such as gastric banding or malabsorption such as Roux-en-Y gastric bypass). Bariatric surgery, particularly malabsorptive procedures, has been associated with a two-fold increase in SGA infants although, in spite of nutritional deficiencies, the risk of congenital anomalies does not differ from the general population (23).
TABLE 13.3 2009 Institute of Medicine Recommendations for Weight Gain in Pregnancy (22) | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ||||||||||||||||||
▪ HYPERTENSIVE DISORDERS AND PREECLAMPSIA
Preeclampsia is a syndrome characterized by hypertension and proteinuria after 20 weeks of gestation. Although the molecular basis is unknown, abnormal trophoblastic invasion and abnormal remodeling of spiral arteries are thought to be involved in the pathogenesis (24). Abnormal placentation results in hypoperfusion and placental hypoxia, leading to release of angiogenic factors into the maternal circulation. Endothelial dysfunction causes microangiopathic changes to the maternal kidneys, brain, liver, and placental bed that result in the clinical syndrome of preeclampsia.
Preeclampsia affects approximately 5% to 8% of pregnancies. Major risk factors include extremes of age; nulliparity; multiple gestations; prior history of preeclampsia or the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome); pregestational DM; and the presence of antiphospholipid antibodies. Hypertensive diseases of pregnancy can be classified into four categories (Table 13.4): gestational hypertension, preeclampsia, chronic hypertension, and chronic hypertension with superimposed preeclampsia (25,26). Recently, ACOG published an executive summary that changes some of the historical distinctions and definitions (25).
| ||||||||||||
It is likely that different pathogenic mechanisms are responsible for early-onset preeclampsia (before 34 weeks) compared to lateonset disease. In general, early-onset preeclampsia is associated with FGR and SGA neonates; late-onset preeclampsia more often is associated with infants with normal or LGA birth weights (26). Early-onset preeclampsia has been more closely associated with adverse neonatal outcome and need for premature delivery (27). Since antihypertensive therapy in the setting of preeclampsia does not change the clinical course of disease, routine use is discouraged (28).
Placenta abruption is more commonly seen among pregnant women with preeclampsia than those without preeclampsia (3% vs. 1%). Severely elevated blood pressure values above 160/105 mm Hg and a previous history of abruption are the strongest risk factors for abruption; however, this complication can be seen even with mildly elevated blood pressures. In general, treatment for preeclampsia is delivery. In cases of mild preeclampsia, delivery may be delayed until 37 weeks (29). In the setting of preeclampsia with severe features or HELLP syndrome, delivery usually is indicated after 34 weeks, though expectant management may be utilized in carefully selected cases with supervision of a Maternal Fetal Medicine specialist (30). Prior to 34 weeks, if mother and fetus are stable, delivery can be delayed in order to administer corticosteroids to accelerate fetal lung maturation (30).
Eclamptic seizures can be one of the most serious consequences of hypertensive disease of pregnancy, with high risks of maternal and neonatal morbidity and mortality. Most seizures are self-limiting and last 1 to 3 minutes; fetal bradycardia and abnormal fetal heart rate patterns are common. Immediate delivery is strongly discouraged due to significant risks of maternal morbidity; improvement in fetal status occurs with successful maternal resuscitation and stabilization. Parenteral magnesium sulfate is the first line of therapy to prevent recurrent or new-onset seizures in women with preeclampsia and severe preeclampsia (31). A decrease in fetal heart rate variability and some neonatal depression at birth that usually responds to standard neonatal resuscitation can be seen with maternal administration of magnesium sulfate. Prevention of preeclampsia has been largely unsuccessful (30). Administration of low-dose aspirin has had conflicting results in reducing the risk of preeclampsia, though a mild-to-moderate risk reduction has been demonstrated in some high-risk women (25,30). Supplementation with calcium, vitamin C, and omega-3 has not been shown to prevent preeclampsia in low-risk women (30).
▪ DIABETES MELLITUS
Approximately 6% to 7% of pregnancies are complicated by DM, 90% of which are due to GDM, which is defined as diabetes diagnosed during pregnancy (32). The remainder includes DM existing prior to pregnancy or pregestational DM. Worldwide, rates for both pregestational DM (Type 1 and Type 2) and GDM have increased; the prevalence of GDM is proportional to the prevalence of Type 2 DM in a given population (32,33).
Pregestational DM
Pregestational DM is not unusual among women of reproductive age due to increasing obesity, delayed conception, and treatment successes for women with Type 1 DM. Prepregnancy evaluation for end-organ dysfunction and vascular involvement can help ascertain risks of adverse pregnancy outcomes. Vascular disease or renal involvement confers higher risks of preeclampsia, FGR, and preterm delivery. Hypertension, which occurs in 5% to 10% of women with pregestational DM, may increase risks for preeclampsia, SGA infants, and stillbirth, especially with coexistent renal disease (34,35).
Preconception counseling is critical for women with pregestational DM, since fetal anomalies and stillbirth rates are higher with hyperglycemia and elevated levels of glycosylated hemoglobin at conception and early in the first trimester (15,34). Major congenital anomalies are the most frequent cause of perinatal mortality in infants of diabetic mothers. The most common abnormalities include NTDs, complex congenital heart defects, and skeletal malformations such as sacral agenesis. Preconception folic acid supplementation to prevent NTDs is advised although higher doses, recommended by some, have not been endorsed universally (34). Excellent glycemic control is essential during pregnancy. A common strategy includes diet, exercise, and insulin therapy (multiple daily doses, particularly for women with Type 2 DM, or careful monitoring of insulin pumps in women with Type 1 DM). Sonographic screening for anomalies, with particular attention to the fetal heart, is recommended for all patients and especially for those with poor glucose control. Additional recommendations include serial sonograms for fetal growth and implementation of third trimester antenatal testing. Cesarean delivery is advised for fetuses with estimated fetal weights above 4,500 g to prevent traumatic birth injury (34). During labor, parenteral insulin is administered to reduce the risk of neonatal hypoglycemia after birth. Postpartum, significantly lower insulin requirements exist, and insulin doses need to be adjusted under close supervision.
Gestational DM
Higher rates for gestational DM (GDM) are noted among African American, Hispanic, Asian, Native American, and Pacific Islander women, and those with a previous history of GDM, obesity, sedentary lifestyles, and a family history of DM (34
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
