Childbirth

Abstract

Parthenogenesis is the development of offspring from unfertilized eggs. Parthenogenesis forms a regular part of some sexual life cycles, but there are also many lineages of animals that have given up sexual reproduction and become obligately parthenogenetic. There are a number of genetically different types of parthenogenesis, ranging from gamete duplication, which immediately eliminates all heterozygosity, to apomixis and prezygotic doubling, which both preserve all the heterozygosity that was present in the mother. The existence of successful parthenogenetic lineages demonstrates that sex is not necessary for reproduction and raises the question of why sex exists. Parthenogenetic lineages are often successful in the short term but almost never persist in the evolutionary long term. An influential hypothesis holds that sexual populations persist longer than parthenogenetic populations because they evolve more rapidly in response to environmental challenges such as rapidly evolving parasites and pathogens. But the adaptive significance of sexual reproduction remains an open question, and parthenogenetic lineages play an important role in ongoing testing of this and other hypotheses.

Hormonal Modulation

Birth control choice can be very important in patients with HS. Some patients describe gradually developing HS lesions after starting a new birth control: high-androgen containing OCPs and androgen-only birth control, even in the intrauterine device (IUD) form, can trigger and worsen HS.⁵ Clinicians should inquire of any potential contraindications to a type of birth control, such as having migraines with auras or long-term smoking. Additionally, birth control compliance should be discussed with patients to determine which birth control would be the best option for the patient.

Low-androgen OCPs, such as ethinyl estradiol-drospirenone and ethinyl estradiol-desogestrel, can benefit females who have perimenstrual flares with limited disease. This type of OCP can be used with spironolactone or by itself to prevent flares in this patient group.¹⁹ Copper-containing IUDs do not contain hormones and can also be a birth control option for patients.

Following discussion with patients about birth control, clinicians may determine whether changing birth control is recommended and also whether the patient plans on becoming pregnant in the near future. Patients may have an IUD or birth control implant that they prefer to remove at a later point. If this is the case, the clinician can provide the patient with a list of optimal birth control options once the patient chooses to change birth control.

A. The Birthing Bed

Birthing beds have gained increasing popularity and use in the United States. These beds combine the advantages of the birthing chair (mobility, ease of position change, decreased pain in second stage, improved bearing down) with the advantages of a traditional delivery table (at least for the birth attendant), while being much more comfortable than either the chair or the table. Although expensive to purchase, they are increasingly incorporated into birthing units in hospital and nonhospital settings. These multiposition beds allow a delivering patient to assume a variety of positions and facilitate upright positioning. They have the advantage of equal usability for nontraditional and traditional or operative deliveries.

6.11 Myositis

Seasonal birth patterns were identified in subgroups of patients with myositis, suggesting an etiologic role of early environmental exposures. Some subgroups of patients with juvenile myositis had seasonal birth distributions. Patients with juvenile dermatomyositis with the p155 autoantibody had a birth distribution that differed significantly from that of patients with p155 antibody-negative juvenile dermatomyositis. Patients with juvenile myositis with the HLA risk factor allele DRB1*0301 and patients with myositis with the linked allele DQA1*0501 had a birth distribution significantly different from those without the alleles. Birth distributions seem to have greater seasonality in juvenile than in adult myositis subgroups, suggesting greater influence of perinatal exposures in childhood-onset illness.⁹¹

Birth Does Not Require Exit

Birth and cell-cycle exit are intimately linked, so it is tempting to conclude they must be interdependent (birth needs exit). There is also a model proposing that slowing cell-cycle rate in the last division might also be critical to facilitating birth. Below, we summarize evidence for and against these issues.

In support of the notion that rate reduction favors birth, progenitor cell-cycle length increases with the gradual transition to symmetric production of two RTCs. In zebra fish, the average cell-cycle length does not predict birth, but, of two sibling RPCs, the one with the longer cycle is more likely to differentiate following M-phase. Moreover, amounts of the Cdk-inhibitor drug olomoucine that slow, but do not stop, division are sufficient to trigger premature neurogenesis in the telencephalon. In support of the idea that birth requires exit, the two are temporally coupled and p27^Kip1 induction occurs in the last G2 just prior to RTC birth. Moreover, overexpression of this CKI induces early birth.

The above data are not totally conclusive. Correlations do not distinguish consequence from cause. A longer final cycle in sibling RPCs might reflect deeper migration of the neurogenic partner trying to escape Notch. Olomoucine has targets other than Cdks and importantly, mutations in E2f1, cyclin D1, or Vsx2 that lengthen cell cycle by specific genetic means do not cause a switch to early-born cell types. Thus, whether lengthening the cell cycle is necessary for birth remains moot.

What about exit, is it required for birth? Notch-pathway defects trigger both birth and exit, but this is also a correlation that does not distinguish whether they are interdependent or can be uncoupled. Genetic evidence supports the latter since neurogenesis in the retina, forebrain, cerebellum, and inner ear goes ahead in the absence of Rb and differentiating neurons divide ectopically. As discussed earlier, a subset of ectopically dividing neurons eventually undergo apoptosis, while others survive and exit independent of Rb, and these are the source of sporadic retinoblastoma. However, clearly, birth occurs despite these downstream defects. As with Rb loss, there is also not a shift to late-born cells in retinas lacking p27^Kip1 and/or p19^Ink4. The interphotoreceptor retinoid-binding protein (IRBP) promoter is activated just before photoreceptors are born, yet its use to overexpress cyclin D1 or E2f1 does not prevent initiation of the birth program, and the resulting photoreceptors divide ectopically. CKI overexpression assays suggest that exit can drive birth, yet do not prove that this is the physiologically relevant or necessary route. Indeed, arresting division with hydroxyurea or aphidicolin in Xenopus embryos does not disrupt most central nervous system (CNS) differentiation, indicating that arrest per se is not neurogenic. Perhaps, CKIs induce early birth by affecting a process other than exit, and, indeed, a mutated version of p27^Kip1 incapable of binding and inhibiting Cdks induces neurogenesis through interaction and stabilization of neurogenin 2 (Neurog2 or Ngn2). Alternatively, active cell-cycle components may maintain expression and/or activity of Notch-pathway components and downregulation of the cell cycle would thus block Notch signaling, an intriguing possibility given that E2f regulates the expression of Hes family members.

In summary, while birth and exit are closely coupled, exit is not necessary for birth. They are both induced following escape from Notch-pathway signals, but in an apparently parallel rather than interdependent fashion.

Abstract

Birthing pools have been used for many years during labor to aid relaxation and pain for the mother. Following many studies, water births have been deemed safe for infants as the risk of bacterial colonization of infants does not seem to differ between normal births and water births. The majority of microbiological neonatal infections in water births appear to be related to home births; however, those responsible for birthing pools in healthcare need to be aware of the potential microbiological risks to the mother, the infant as well as staff being exposed to the waterborne pathogens including Legionellae and Pseudomonas aeruginosa.

Changes in Pulmonary Circulation

Birth is accompanied by dramatic vascular changes. The lung shifts from receiving less than 10% of the cardiac output during fetal life to receiving practically all of it after birth. To a great extent, this change is due to the closure of the ductus arteriosus, which in fetal life permits a large fraction of the blood of the pulmonary trunk to bypass the pulmonary circulation, and to the drop in resistance of the pulmonary vessels (Figure 2). Because the ductus arteriosus enters the aortic arch, its postnatal closure reduces blood-flow to the descending aorta, in favor of the upper body and brain.

Figure 2. Schematic representations of the main features of cardiopulmonary circulation before birth (left) and after birth (right). Numbers indicate the approximate changes in blood flow occurring at birth as the result of lung expansion and oxygenation.

The first breath and the onset of continuous ventilation play a crucial role in the cardiovascular changes accompanying birth, mostly because of two mechanisms – lung expansion and oxygenation. The increase in lung volume, by itself and independent from the rise in oxygen pressure, increases pulmonary blood-flow approximately fivefold, according to animal experiments. This may seem astonishing given that lung volume does not differ much before and after the first breath; in fact, the volume of the fetal liquid-filled lung is not lower, and most probably larger, than that of the air-filled postnatal lung. However, after birth, the surface tension created at the air–liquid interface reduces the pressure in the lung interstitial tissue, which promotes vascular expansion and a decrease in pulmonary vascular resistance. Lung ventilation also promotes the secretion of pulmonary prostaglandins, with vasodilating effects. The importance of the rise in oxygen levels in lowering pulmonary vascular resistance has been appreciated for a long time. Sustained hypoxia delays this process, leading to right ventricular hypertrophy. It also seems that the respiratory alkalosis accompanying the onset and establishment of pulmonary ventilation contributes to the vascular adjustments at birth.

Birth Trauma

Birth-related fractures are common, with the clavicle most frequently injured. These injuries occur in infants delivered both vaginally and via caesarian section. Long-bone fractures, classically associated with vaginal delivery of breech presentation, are now seen with increasing frequency in caesarian breech deliveries because planned caesarian delivery has been shown to reduce perinatal and infant mortality in breech pregnancies, and this method of delivery is now preferred in those cases (Fig. 21.12). Fractures secondary to caesarian delivery are, however, still uncommon. In one series, only two fractures were identified in 425 infants after difficult caesarian delivery for breech presentation. Posterior rib fractures have been described in birth-related trauma of very large infants after difficult vaginal deliveries. O’Connell and Donoghue (2007) described three neonates who were found to have CMLs after routine uncomplicated caesarian delivery. Birth-related spine, skull, mandibular, and epiphyseal injuries have also been reported. When discovered before discharge after delivery, these injuries are easily associated with birth trauma. Discovery of these injuries later in the neonatal period becomes more complicated, but in many cases a history of difficult delivery can help distinguish birth trauma from child maltreatment.

Birth-related brachial plexus injuries (obstetric brachial plexopathy)

Birth-related BP injuries (BRBPI) are the result of relatively long-lasting traction forces exerted during delivery. A systematic literature review of the available natural history studies on the prognosis for BRBPI (Pondaag et al., 2004) concluded that the percentage of children with residual deficits is 20 to 30%. BRBPI almost always involves traction of the C5 and C6 nerve roots, resulting in weakness of shoulder function and elbow flexion. Additional involvement of C7, C8, and T1 roots affects elbow extension and wrist and hand function (Borrero and de Pawlikowski, 2005; Carlstedt, 2008). The incidence of BRBPI lies between 0.42 and 2.9 per 1000 live births (Bodensteiner et al., 1994; Bisinella et al., 2003; Birch, 2009). There is a marked variability in the degree of final functional recovery, but those with good and poor outcome cannot be told apart reliably shortly after birth: most infants with BRBPI initially present with paralysis regardless of the severity of the underlying nerve lesion. Only time reveals whether spontaneous recovery does or does not occur. Early identification of severe cases, i.e., those in which spontaneous recovery does not occur, is of paramount importance for several reasons. Firstly, prolonged denervation in BRBPI exacerbates the damage of the original nerve trauma: it leads to end organ atrophy, bone growth disturbances, joint incongruency (Carvalho et al., 1997), contracture formation, and possibly central apraxia (Birch et al., 2005). Secondly, early recognition of severe cases allows early intervention, setting the stage for optimal functional recovery. Therapeutic options to prevent joint contracture formation are vigorous physical therapy, splinting, and botulinum toxin. In selected cases, reconstructive nerve surgery is performed to restore anatomical connections so axonal outgrowth is unimpeded. Results of nerve surgery are better when performed early, to reduce the time end organs are denervated. Finally, tendon transfers or osteotomies are usually carried out at a later age to improve arm function. Such treatment programs require a multidisciplinary approach and expertise usually only available in a few specialized centers. Fortunately, spontaneous recovery is satisfactory in the first months of life in most cases, in whom routine physical therapy will suffice.

A major problem is how to select those infants, shortly after birth, who will form the aforementioned 20–30% with a poor prognosis. A satisfactory test for this selection is currently not available. Results achieved by surgery are claimed to be superior to the outcome in nonoperative treated subjects with equally severe lesions (Gilbert and Tassin, 1984; Waters, 1999; Xu et al., 2000). However, this comparison relied on historical controls (Kline, 2000) and there is as yet, no randomized controlled study (Bodensteiner et al., 1994; Kay, 1998). Determining the lesion present may only become apparent over time, but time cannot be wasted as the interval between nerve trauma and reconstruction is inversely related with the outcome of reconstruction. Early surgery is, therefore, preferred above delayed surgery. At present, the earliest accepted time at which severe lesions can be determined is 2 to 3 months of age. Paralysis of the biceps muscle at 3 months, especially with wrist drop, is associated with a poor prognosis (Tassin, 1983) and is considered an indication for nerve surgery by some authors (Gilbert and Tassin, 1984; Kawabata et al., 1987; Clarke et al., 1996; Birch et al., 2005; Waters, 2005). However, biceps paralysis at age 3 months does not preclude satisfactory spontaneous recovery (Michelow et al., 1994; Waters, 1999; Smith et al., 2004; Fisher et al., 2007). Additionally, biceps muscle testing may not be reliable in infants (Clarke and Curtis, 1995; Borrero and de Pawlikowski, 2005; Fisher et al., 2007). Alternative tests (Xu et al., 2000; Bisinella et al., 2003; Borrero and de Pawlikowski, 2005) are complex or are done at an even later age.

Preoperative ancillary investigations consist of ultrasound of diaphragm excursions to assess phrenic nerve function and CT-myelography under general anesthesia to detect root avulsions (Walker et al., 1996; Chow et al., 2000). Numerous reports have been published concerning results of nerve reconstructive surgery of birth BRBPI. It is well documented that improvement of outcome can be obtained following primary repair. Useful reanimation of the hand was obtained in 69% of patients (Raimondi Score ≥ 3) (Malessy and Pondaag, 2009).

Minerals and Calciotropic Hormones

Birth provokes changes in serum minerals and calciotropic hormones that are schematically depicted in Figure 63.5. There is a 20–30% fall in serum calcium and ionized calcium, followed by an increase to adult values over the succeeding 24 hours.⁵⁶ In one study, the ionized calcium fell from a mean cord level of 1.45 mmol/l to 1.20 mmol/l.⁵⁶ The mode of delivery may also influence the fall in calcium, because babies delivered by elective C-section had lower blood calcium and higher PTH at birth compared to babies delivered by spontaneous vaginal delivery.¹²⁷ In rodents, a 40% fall in blood calcium occurs soon after birth. In humans and rodents, phosphorus increases over the same interval and then declines as the serum calcium rises.

FIGURE 63.5. Schematic illustration of the longitudinal changes in calcium, phosphate, and calcitropic hormone levels that occur during the neonatal period in humans.

Normal adult ranges are indicated by the shaded areas. The progression in PTHrP levels has been depicted by a dashed line to reflect that it is speculative.

Reproduced with permission from¹,©1997 The Endocrine Society.

Following and likely prompted by the initial decline in ionized calcium and rise in serum phosphorus concentrations, parathyroid function normally awakens from the suppressed state of fetal development. In human babies, PTH increases during the first 24 hours and precedes a rise in calcitriol.⁵⁶ Similarly in rodents, PTH increases to adult normal values by 24–48 hours after birth, and calcitriol lags behind PTH in increasing to adult values.⁵²

The neonate will be born with 25(OH)D levels within 75–100% of the maternal value, and a calcitriol level that is low compared to the mother.^65–69 Cord blood calcium is normally no different between babies born of vitamin D-replete and severely vitamin D-deficient mothers; the same is true in animal models of severe vitamin D deficiency and loss of vitamin D receptor or Cyp27b1.² But in the days to months after birth, disturbances in vitamin D metabolism can begin to manifest as hypocalcemia or rickets.^2,70 Breast milk normally contains very little vitamin D or 25(OH)D, and this is why exclusively breastfed babies are at higher risk of vitamin D-deficient rickets as compared to babies fed vitamin D-supplemented formula. In order to avoid vitamin D deficiency, breastfed babies need vitamin D supplements or sunlight exposure.