Anticipating problems

There are a number of pointers that indicate increased risk to the fetus and newborn. A careful history is key, including maternal obstetric, medical, and family history, medications, antenatal screening tests and sonography, pattern of fetal growth, intrapartum progress, and mode of delivery.

Early communication with the neonatal team, well in advance of delivery, is good practice and can help ensure a robust postnatal plan of management is formulated for the newborn. In many cases, the obstetrician is faced with the complex task of balancing maternal benefit and fetal risk. A common example is the timing of delivery in pre-eclampsia where maternal risks must be balanced against the risks to the neonate of preterm delivery. Current evidence helps inform such debate with data from the recent HYPITAT-II trial (3) indicating a more than threefold increase in neonatal respiratory distress syndrome in moderately preterm infants between 34 and 37 weeks' gestation, born to mothers with non-s evere hypertensive disorders of pregnancy, randomized to immediate delivery as opposed to expectant management (relative risk (RR) 3.3; 95% confidence interval (CI) 1.4-8.2; P = 0.005). The key principles of management, whatever the obstetric condition or concern, are multidisciplinary discussion, shared decision-making, and careful documentation of the rationale for decisions, especially in situations where evidence to guide practice is uncertain.

Preterm birth

The global problem

One in ten babies are born preterm (4) (Table 37.2) with the preterm birth rate continuing to rise globally, especially in low-income countries (5). Currently over 60% of preterm births are in the low- resource, low-income countries of southern Asia and sub-Saharan Africa (5). Though mortality has fallen, there is growing recognition of the increased risk of lifelong morbidity in survivors.

In addition to well-recognized respiratory and neurodevelopmental morbidity, a growing research literature points to the adverse impact of preterm birth on cardiometabolic health, longevity, and reproductive outcomes. The prevention and management of preterm birth is thus an important population health issue.

Managing preterm birth from the neonatal perspective

The unexpected birth of a preterm infant is not uncommon, indicating the importance of ensuring that every birth facility has expertise in the basic principles of care. When preterm birth is anticipated, every attempt should be made to transfer the mother to a facility that is able to provide appropriate care for both the mother and her newborn infant. There is growing evidence that care in a high-volume facility improves survival for preterm infants at less than 33 weeks' gestation, an effect that is magnified for extremely preterm infants (birth. Though this advice will vary depending on the gestation of the fetus and other factors (e.g. multiple pregnancy, fetal sex, growth restriction, and congenital anomalies), counselling should ideally be a joint discussion with both neonatal and obstetric personnel. Where possible, information should be provided on more than one occasion verbally, and in writing. It is important that the

Table 37.1 Definition of perinatal, neonatal, postneonatal, and infant mortality

Mortality indicator	Definition
Stillbirth	A baby born after 24 or more weeks completed gestation and who did not, at any time, breathe or show signs of life
Perinatal mortality	Stillbirths and deaths less than 7 days of age per 1000 total births
Neonatal mortality	Deaths under 28 days of age per 1000 live births
Post neonatal mortality	Deaths between 28 days of age and 1 year of age per 1000 live births
Infant mortality	Deaths under 1 year per 1000 live births

information is provided in a clear, consistent, and empathetic way and that decision-making, especially at the limits of gestational viability, genuinely reflects parental views.

An opportunity should be provided for the family to visit the neonatal unit.

Preterm health outcomes

Several large population data sets exist such as the EPICURE (8), EXPRESS (9), and EPIPAGE (10) studies and such data can be helpful in providing information about health outcomes to families. Local data on preterm outcomes may also be available but should be used with caution because of the small numbers of extremely preterm infants in any given hospital. In the United Kingdom, the EPICURE 2 cohort provides short- and long-term population-based health outcomes for preterm infants between 22 and 26 weeks' gestation born in 2006 (8). In this cohort comprising preterm infants less than 26 weeks' gestation, 68% developed bronchopulmonary dysplasia (defined as the need for supplemental oxygen at 36 weeks postmenstrual age), 13% had evidence of serious abnormality on cranial sonography, and 16% required laser therapy for treatment of retinopathy of prematurity. Rates of severe impairment at 2-3 years of age were 26% for children born at 22-23 weeks' gestation, 15% at 24 weeks, 14% at 25 weeks, and 10% at 26 weeks. Though population data cannot necessarily be applied to an individual pregnancy, they are nonetheless useful when used in conjunction with a sensitive discussion about pregnancy management options and foreseeable problems for the newborn infant.

Antenatal interventions of benefit to the preterm infant

Antenatal steroids

In the 1960s and 1970s, studies in fetal lambs by Liggins and Howe demonstrated the importance of cortisol in fetal lung maturation

Table 37.2 Definitions of extremely, very, moderate and late preterm birth

Preterm birth

but whose growth is faltering. The widely used Hadlock fetal growth curves were constructed 25 years ago with data from less than 400 ‘predominantly middle-class white patients’ (20) and their effectiveness in identifying at-risk infants in populations around the world is uncertain.

The World Health Organization postnatal growth charts developed from longitudinal measurements in infancy show healthy babies across diverse countries that include India, Brazil, and the United States, to have a similar pattern of growth (21). This suggests that all human fetuses, if not constrained by maternal factors, might also exhibit a similar growth pattern. Charts based upon measurements from women around the world have been developed but until maternal health and maternal size are optimal, and until the fetal growth pattern resulting in optimal lifelong health has been identified, these should be considered as a reference, rather than a standard (22). For the moment, a reasonable approach to selecting a reference would be to base this on the sensitivity and specificity for detecting cases of perinatal mortality and morbidity in specific populations.

Caesarean section

Birth by caesarean section is increasing in many parts of the world. Factors suggested as underpinning this trend include maternal choice, social expectation, rise in maternal obesity, a rise in age at first pregnancy (with accompanying comorbidities), and an increased number of mothers with a previous history of caesarean section. Other factors, set against the increased safety of caesarean section as a procedure, include medicolegal concerns, defensive medicine, and the financial incentives of private practice. There are clearly situations where caesarean section is life-saving for either the mother or the fetus, or both, yet paradoxically the procedure is insufficiently available in many parts of the world where both maternal and neonatal morbidity are highest (23).

The short-term neonatal morbidities associated with birth by caesarean section (Box 37.1) are well recognized. To some extent these can be mitigated by the administration of antenatal steroids for elective caesarean section before 38⁺⁶ weeks’ gestation (24). It is perhaps less well known that birth by caesarean section is associated

Box 37.1 Short-term newborn health effects related to birth by caesarean section

• Increased rate of neonatal unit admission

• Increased respiratory morbidity

• Impaired thermal adaptation

• Impaired metabolic adaptation (e.g. hypoglycaemia)

• Reduced initiation of breastfeeding with lower breastfeeding initiation (25).

Further, the practising obstetrician needs to also be aware of the emerging evidence relating to possible longer-term health implications of birth by caesarean section (26). Epidemiological studies point to an association between birth by caesarean section and increased body mass index z-score in childhood (0.20 units; 0.07-0.33 increase) (27), diabetes (OR 1.23; 95% CI 1.15-1.32) (28), and childhood asthma (OR 1.20; 95% CI 1.14-1.26) (29). Mechanistic studies are rare and causality has not been established. However, plausible determinant pathways include alterations in the infant microbiome that drive increased intestinal energy harvesting, and epigenetic effects induced by exposure to the inflammatory and endocrine milieu of labour on metabolic and/or immune development.

Multiple births

There has been a fourfold increase between 1992 and 2006 in artificial reproductive technology (ART) such as in vitro fertilization (IVF) and intracytoplasmic sperm injection treatment in the United Kingdom (30). This is attributed, at least in part to increased availability, access, and affordability of ART to patients. In addition, the range of ART available has increased to include preimplantation genetic diagnosis and oocyte cryopreservation. Babies born by ART have a significant impact upon neonatal services because of the increased risk of preterm birth, which in turn is associated with a fivefold higher neonatal mortality when compared to singleton pregnancies (11.5 vs 2.4:1000 live births) (31). ART has a major impact upon the numbers of preterm births, and is a growing strain upon neonatal services, especially in countries that have poor regulatory oversight of such practices. In addition, though causality has not been established, there is concern regarding the association between ART and congenital anomalies, epilepsy, genomic imprinting disorders, and an observed fourfold increase in cerebral palsy (32). In the United Kingdom, the Human Fertilisation and Embryology Authority (HFEA) has provided guidance to clinicians and prospective families and requires centres to have clear strategies to reduce multiple births by defining criteria for the use of single embryo transfer.

From 2008 to 2010 there has been an increase in the proportion of single embryo transfer IVF pregnancies from 4.8% to 14.7% and a parallel reduction in the proportion of multiple pregnancies from IVF (from 26.7% to 22.0%) (33). HFEA regulation and codes of practice remain an important strategy to ensure that multiple birth-related preterm morbidity and potential adverse health outcomes for the child are mitigated. There is also an increasing call for the health outcomes of children born by newer types of ART to be monitored through the establishment of formal registries.

Congenital anomalies

Congenital anomalies account for approximately 27% of all neonatal deaths in England and Wales (34) and approximately 4.4% of neonatal deaths globally (276,000 neonatal deaths were attributed to congenital anomalies in 2013) (35). Congenital anomaly registers (e.g. National Congenital Anomaly and Rare Disease Registration Service (NCARDRS), British Isles Network of Congenital anomalies register (BINOCAR), European Surveillance of Congenital Anomalies (EUROCAT)) are important means of detecting the prevalence of congenital anomalies, monitoring trends over time and the impact of interventions. United Kingdom data indicate a decline in congenital anomalies between 2007 and 2011 from 264.7 to 249.5 per 10,000 total births (36). Congenital anomalies are important, as though rare individually, as a group they are relatively common. They are also associated with significant long-term disabilities and have considerable impacts upon the affected individual and the family. Maternal risk factors include low socioeconomic status, consanguinity, maternal age, antenatal infections (e.g. syphilis, rubella), diabetes, tobacco, alcohol, illicit drug use, iodine deficiency, and folic acid deficiency. However, antenatal detection rates are anomaly specific (36, 37) as illustrated in Table 37.3. Hence, all newborn infants should receive a thorough physical examination following birth. This is particularly so for the detection of serious forms of congenital heart disease where lack of detection (either antenatally or postnatally) can be life-threatening and associated with increased morbidity. Though antenatal detection rates of congenital heart disease are improving (38), the combination of antenatal screening for congenital heart disease and postnatal clinical examination still misses approximately 50% of cases (39). Therefore, to improve detection of these conditions, many countries now recommend universal oxygen saturation screening for all newborns as a moderately sensitive (75%), highly specific (99.9%), cost-effective method in parallel with antenatal sonography and clinical examination (40). This involves applying a pulse oximeter probe to all newborn infants (usually between 4 and 24 hours after birth). A positive test is defined as an oxygen saturation of less than 95% in either pre- or postductal oxygen saturation or a greater than 2% difference between pre- and postductal oxygen saturations. Newborns with a positive test can then undergo further evaluation to establish the cause of their hypoxia. The test has extended utility in that in addition to the detection of asymptomatic congenital heart disease, newborn infants with other pathologies that might require neonatal intervention (e.g. sepsis, meconium aspiration syndrome) may also be identified.

When congenital anomalies are detected in the antenatal period, the clinical team is able to discuss management options with the

Table 37.3 Antenatal detection rates for selected congenital anomalies

Anomaly	Antenatal detection rate (%)
Anencephaly	96.9
Neural tube defects	95
Cardiac anomalies	35-49.2
Cleft lip ± palate	65-74.5
Congenital diaphragmatic hernia	64-73
Bilateral renal agenesis	89.3
Lethal skeletal dysplasia	94.4
Gastroschisis	91.7-100
Exomphalos	90-92.3
Chromosomal	56
Edward syndrome	76.6
Patau syndrome	82.7

Source data from Springett A, Budd J, Draper ES, Kurinczuk JJ, Medina J, Rankin J, Rounding C, Tucker D, Wellesley D, Wreyford B, Morris JK. Congenital Anomaly Statistics 2012: England and Wades. London: British Isles Network of Congenital Anomaly Registers; 2014 and Kurinczuk JJ, Hollowell J, Boyd PA, Oakley L, Brocklehurst P₁ Gray R. The Inequalities in Infant Mortality Project Briefing Paper 4: The Contribution of Congenital Anomalies to Infant Mortality. National Perinatal Epidemiology Unit, University of Oxford (June 2010).

parents in advance of birth. It is good practice to involve neonatolo- gists (and other relevant specialities, e.g. geneticists) in counselling. This enables decisions to be made about continuation of pregnancy versus termination, helps the family to come to terms with the diagnosis and be provided with relevant information about the condition, and to plan the timing and location of the delivery (e.g. in a centre with surgical neonatal expertise).

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Source: Arulkumaran S., Ledger W., Denny L., Doumouchtsis S. (eds.). Oxford Textbook of Obstetrics and Gynaecology. Oxford University Press,2020. — 928 p.. 2020

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