Open access peer-reviewed chapter
The demographic characteristics of the study participants.
Abstract
Prolonged labor is a common finding in labor wards. One known cause is that the smooth muscle of the uterus did not contract well enough, so the cervical opening and head position failed to follow the progress line in the partograph. Few detailed data exist regarding this because we usually directly give patients more contraction agents, such as oxytocin and amniotomy, rather than look for the cause. Tapping into a mother’s natural strength is a gentler and just as practical approach. Calcium is known to affect smooth muscle contraction. Thyroid hormone is also known to affect the calcium level in the body. This chapter ponders the question, “How do calcium and thyroid hormone solve prolonged labor problems?” We consider prepared antenatal care with normal calcium and FT4 levels supplementation worth a trial to have the chance of normal prolonged labor without augmentation.
Keywords
- prolong labor
- labor
- calcium
- thyroid
- uterine contraction
1. Introduction
Prolonged labor is common during obstetric practice and is consequently the most common intrapartum indication for cesarean section [1, 2]. Cesarean section is known to have higher postoperative complications than vaginal delivery. Meanwhile, vaginal delivery with a prolonged course itself also has maternal and fetal side effects, such as trauma, low Apgar score, and puerperal infection [3, 4, 5]. Both bring a dilemma to practicians as to where or when prolonged labor should be allowed to avoid the expense of postoperative complications of cesarean section [3, 5, 6].
This condition is very challenging to diagnose and manage [6, 7]. Sometimes, many practitioners cannot estimate the speed of physiological labor. Therefore, they cannot decide to do specific management. Friedman [8] established a standard baseline to evaluate labor progress. It helps to form prolonged labor management protocols. Philpott [9] also designed a partograph to help monitor the labor progress based on Friedman’s curves. The prolonged first stage of labor is often defined as crossing the action line of the partograph or labor progress curve in the first stage of labor, after the latent phase, and before reaching full dilatation of the cervix [9].
The American College of Obstetricians and Gynecologists (ACOG)/Society for Maternal-Fetal Medicine criteria for diagnosis of labor arrest are: (1) the dilatation of the cervix is 6 cm or more; (2) ruptured of the membrane found; and (3) cervical changes after at least 4 hours with adequate contraction or at least 6 hours of oxytocin administration with inadequate uterine activity are not found. Indeed, prolonged labor can be judged only in retrospect [10].
Most of the time, inadequate uterine contraction is the first reason to be suspected when prolonged labor occurs other than cephalo-pelvic disproportion (CPD). Since CPD is a per-exclusion diagnosis that is established in the presence of adequate uterine contractions, many practitioners directly and quickly augment contraction [11, 12]. The ACOG also made clinical practice guidelines for amniotomy, oxytocin, and other interventions to manage prolonged labor [10]. All these actions are intended to make labor adhere more to the partograph, and an intervention to expedite birth is taken rather than to look at the cause in more detail.
By this clinical decision, some women with slower progress of dilation (even though it is normal) are prone to have an intervention with its consequences (fetal distress or infection). With the recent advanced methods of fetal monitoring during labor (such as continuous CTG), a longer duration of labor than a partograph should be more feasible.
However, the pathogenesis of prolonged labor is poorly described, primarily due to the lack of research in this area [6]. There is still limited discussion about preventing prolonged labor or better preparation during antenatal care. Our perinatal statistics demonstrate that prolonged labor is possible as long as standard fetal monitoring is maintained during labor. This chapter will discuss the role of calcium and thyroid in prolonged labor.
2. Prolonged second stage of labor
The prolonged second stage of labor differs from the prolonged first stage. The typical second stage of labor varies in duration from minutes to many hours, but the optimal limit on the duration of the second stage is unknown [5]. A more prolonged second stage of labor brings a significant increase in the risk of fistula, vaginal injury, and postpartum hemorrhage (PPH) [5]. Second-stage cesarean birth is also more challenging to do and brings more maternal operative complications, as with an impacted head of the fetus in the pelvis [13]. However, clinicians should outweigh the risks and benefits of cesarean section in the prolonged second stage of labor compared to vaginal birth.
The National Institute for Health and Care Excellence (NICE) advises intervention after three hours of active second stage for women giving birth for the first time (nulliparous) and two hours for multiparous [14]. However, a systematic review found no consistent evidence connecting the duration of the second stage with adverse outcomes [15]. The study was affected by confounding data and the broad categorization of the second stage duration. However, after adjusting or confounding factors, the odds of NICU admission reduced with increasing duration of the second stage [15].
3. Active management of labor
Active management of labor was first intended to reduce the rate of prolonged labor by making sure all women adhere to partograph or faster [16, 17]. This would make obstetricians make fewer decisions based on inadequate uterine contractions or slower dilatation of the cervix [16, 18, 19, 20]. Three large randomized controlled trials compared a policy of active management of nulliparous labor with routine management [19]. In these studies, active management included precisely diagnosing labor, performing early amniotomy, conducting vaginal examinations frequently, and administering high-dose oxytocin to augment slow labor progress characterized by less than 1 cm of cervical dilatation per hour [19, 21]. All three studies have reported a reduction in the duration of labor, and two found reduced maternal infectious morbidity [19, 21, 22]. Therefore, the issue of whether a policy of active management of nulliparous labor can reduce cesarean section rates is still unresolved [19, 23, 24]. One study found a reduced cesarean section rate with active labor management, but only after controlling for confounding factors [19, 23].
The criticism of active labor management is related to more interventions during labor rather than understanding the diversity of labor progress in every patient possible [19, 23]. This resulted in a more medicalized birth process rather than looking into the cause over which women have less control [19, 23, 24]. Meta-analyses have concluded that neither of these single interventions effectively reduced cesarean section rates [19, 23]. The expected rate of increase (1 cm per hour) in all labor is standardization and has not proven to be applicable in all first labors, nor does standardize the 12-hour time allocation in partograph [19, 24].
4. MRI and other methods to predict prolonged labor
Vaginal delivery remains needs fetus–pelvis fit proportion. Previous studies have demonstrated that MRI can be reliable in evaluating labor outcomes [25, 26, 27]. Fox et al. [28] have attempted to validate MRI pelvimetry in women with previous cesarean sections. The obstetric conjugate is the most significant predictive pelvic measurement among all MRI pelvimetry parameters, as it shows a strong positive correlation with vaginal delivery [29].
Klemt et al. [30] used an obstetric conjugate of 12 cm to represent a sufficient pelvic inlet for the trial of labor. Meanwhile, Joyce et al. [31] reported that a 3400-g weight fetus requires minimal obstetric conjugate of 10 cm to pass through the birth canal. However, the applicability of these findings is limited by racial differences. A higher body mass index (BMI) may significantly affect soft-tissue pelvic volume, which is closely associated with prolonged labor [29]. Li et al. [32] wrote that women with lower BMIs as well as larger interspinous distance (ISD) and intertuberous distance (ITD) were more likely to have a successful vaginal delivery. The ISD represents the mid-pelvis is particularly important, as its narrowing can obstruct the fetus’ internal rotation, hindering the descent of the head [33]. Women with lower BMIs, smaller fetal biparietal diameter (BPD), and AC should be allowed to continue trying labor under close monitoring. MRI pelvimetry could be a valuable tool for selecting nulliparous women who can undergo a trial of labor [32].
5. Uterine muscle contractility, oxytocin, and calcium
Figure 1 describes the mechanism of uterine contraction. Uterine contraction starts by activating a second messenger of prostaglandin and oxytocin, which are G protein-coupled receptors (GPCR) on the cell membrane [35]. GPCR then triggers a cascade of events that release calcium mostly from the sarcoplasmic reticulum [35]. The intrinsic ionic change also triggers ligand-specific calcium channels. It causes more calcium influx, so thereby strengthening the uterine contractions [35].
Figure 1.
The mechanism of uterine contraction [34].
Pehlivanoğlu et al. [35] concluded that calcium released from the sarcoplasmic reticulum is rapidly depleted compared to the extracellular calcium from calcium channels. Loftus et al. [36] demonstrated that calcium influx by ligand-type channel significantly contributes to the depolarization-excitatory phase of the uterine myocyte. Increased intracellular calcium and extracellular Cl– concentration also activate Ca2+-activated chloride (Cl–) channels (CaCCs) [27]. The CaCCs then depolarize the myometrial membrane and activate L-type calcium channels [37]. Enhancing uterine contractility by calcium through various pathways offers a physiological basis for using calcium supplementation to improve uterine contractions and reduce the risk of labor dystocia [38].
The frequent use of oxytocin aims to induce or augment labor. A decrease in uterine contraction, even with oxytocin augmentation, may be due to relative calcium insufficiency [39]. Mcalpine et al. [6] reported that exposure to synthetic oxytocin may contribute to oxytocin receptor desensitization, reducing endogenous oxytocin secretion and decreasing uterine contractions.
6. Muscle and lactic acid
Lactic acid can accumulate as metabolism shifts from aerobic to anaerobic during uterine contractions, leading to contraction fatigue. This lactic acid is found in the myometrium as amniotic fluid lactic (AFL). Elevated levels of AFL are linked to labor dystocia and may increase the chance of requiring cesarean section [40]. These findings led to an intervention of administering bicarbonate, a base that alkalinizes the amniotic fluid, reducing AFL levels and restoring the uterine pH for adequate myometrium contractility [41]. Wiberg-Itzel et al. [42] concluded that sodium bicarbonate intervention significantly reduced AFL levels and increased the spontaneous vaginal delivery rate in the group of 200 randomized patients.
Seyedi et al. [41] found that patients receiving sodium bicarbonate and oxytocin had higher rates of spontaneous delivery in cases of prolonged labor. The intervention group had fewer cesarean births and second stages of labor than the control group [41].
7. Normal calcium and labor
Total calcium serum typically ranged at 2.2–2.5 mmol/L, roughly half of this being ionized calcium (average 1.1 and 1.5 mmol/L) [43]. However, it may not accurately reflect the ionized calcium level. The calcium level in the serum might increase the reserve and the influx of extracellular calcium into the intracellular, contributing to better contractions. Therefore, it is hypothesized that increased serum calcium during labor may promote more effective contractions [44].
Calcium homeostasis in the non-pregnant individual is relatively simple [45]. Pregnant women have lower maternal serum levels due to increased fetal demand, estrogen, hemodilution, and uteroplacental calcium transport mechanisms [45, 46, 47]. This results in fetal hypercalcemia but hypocalcemia in maternal serum calcium, mainly during the third trimester. Hyperventilation during labor might cause respiratory alkalosis and a shift in the acid-base balance [48, 49]. This results in calcium ions binding with albumin and creating fewer acid compounds [48]. Further, alkalosis inhibits tissue response to parathyroid hormone and reduces serum calcium concentration [48].
A study measured the calcium levels of two groups who had scheduled cesarean and had no labor signs at 38 weeks gestation [50]. Levels of serum calcium were higher in pregnant women who delivered vaginally than those who had scheduled cesarean delivery. The calcium levels in the umbilical vein of the newborns born after spontaneous labor were higher than those after a cesarean section [50].
8. Calcium administration during labor
Danforth and Ivy et al. showed that postpartum uterine contractions do not occur in dogs and rabbits when calcium levels are low [51]. Dystocia in the parturient bitch is also resolved by slow intravenous administration of calcium gluconate [48, 51, 52]. Calcium plays an essential part in preventing uterine dystocia by its quieting effect on the sympathetic nervous system and producing regular uterine contractions [35].
Two mid-twentieth-century studies reported that pregnant women with normal calcium levels experienced shorter labor and lower morbidity than a comparable control group [53, 54]. It concludes that an increase in ionized calcium is essential for spontaneous onset of labor. The changes in the ionized to non-ionized calcium ratio may have contributed to the stronger uterine contractility [54]. Intravenous calcium gluconate was a significant factor in promoting regular and effective uterine contractions [54].
Two dated but significant studies verified labor enhancement through calcium therapy [53, 54]. In 1947, Grier [53] concluded that patients who were given calcium gluconate and intramuscular oxytocin experienced shorter labor than the average labor. 1954, Whyte [54] determined that combining calcium gluconate and oxytocin is a safe and effective approach for labor induction. In that study, the 200 participants who received that combination experienced a shorter duration of labor compared to the standard protocol [54]. No maternal mortality or neonatal deaths attributable to induction were recorded in either study [53, 54].
9. Calcium as a potential intervention to prevent postpartum hemorrhage
Postpartum hemorrhage (PPH) frequently happens following exogenous oxytocin augmentation and its consequence of receptor desensitization to oxytocin. Oxytocin receptor sensitivity is dependent on free-ionized calcium. Optimizing serum calcium can minimize the effects of receptor desensitization to oxytocin and enhance uterine contraction, especially in augmented prolonged labor, which is a risk factor for PPH [55]
For instance, patients with PPH who did not respond to oxytocin were found to have improved uterine contractions and less bleeding after receiving calcium gluconate intravenously. Wang and Lu [56] reported that women with low serum calcium levels were at a higher risk of PPH within 2 hours postpartum than normal serum calcium patients, suggesting that calcium could help prevent uterine atony. Qin and Gou [57] showed that administration of 10 ml of 10% calcium gluconate at the time of labor, especially near full cervical dilatation, had increased mean serum calcium at the time of fetal head crowning. It leads to fewer cases of primary PPH. They also found that the risk of PPH was increased when the antepartum calcium levels in serum were below 1.05 mmol/L. These findings align with the results of the present study, where patients with primary PPH due to uterine atony had a mean serum ionized calcium level of 2.8 ± 0.35 mg/dL, which is lower than this critical value [57].
10. Thyroid and calcium
Thyroid hormones are essential for normal reproductive function and labor course. Hypothyroidism during pregnancy is highly associated with miscarriage, preterm labor and delivery, intrauterine growth restriction (IUGR), and neonatal death [58]. In animal studies, hypothyroidism is associated with dysfunction in the pituitary-ovarian axis and impaired follicular maturation. The endometrium, myometrium, and uterine weight volumes are lower in hypothyroid rats [58].
The catabolic effect of thyroid hormone to increase bone mineral resorption and calcium loss regulates calcium homeostasis [59, 60]. The synchronized function of the parathyroid hormone, vitamin D, and calcitonin also regulate calcium serum [59, 60]. Thyroid hormone inversely inhibits parathyroid hormone secretion, increases the osteoclast activity, and decreases the calcium excretion [59, 61]. Patients with hyperthyroidism tend to have low levels of PTH with an inverse effect on serum calcium levels [59, 60, 61, 62]. Thyroid hormone also influences uterine muscle contractility because thyroid receptors are found in the uterine smooth muscle nuclei. The thyroid also acts directly on the smooth vascular muscle as a vasodilator that influences the peripheral vascular system. Thyroid hormone treatment can rapidly reverse higher systemic vascular resistance in pregnant women with hypothyroidism [58].
Free thyroxine (FT4) and thyroid stimulating hormone (TSH) have a role in releasing oxytocin in the labor course. In the third trimester, pregnant women with elevated TSH and Thyroid Peroxidase Antibody (TPOAb) followed by low FT4 are associated with a prolonged duration at the first stage of labor [59]. TPOAb has a role in catalyzing tyrosine iodization and its coupling with iodotyrosyl residues. Cambell et al. wrote that forming free triiodothyronine and FT4 will regulate the release of oxytocin [59, 61].
11. Jakarta experience
Considering these observations, prepared antenatal care aimed at normal calcium and FT4 levels was considered worth a trial. This study aimed to determine whether the women with calcium and levothyroxine supplementation in antenatal care would have normal prolonged labor with no increased risk of maternal and fetal complications. This would allow some women to have more natural progress in labor with optimal outcomes.
12. Material and methods
This retrospective study was conducted in the Department of Obstetrics, Cipto Mangunkusumo Central National Hospital, Jakarta, and Hermina Hospital, Bekasi, between January 2020 and September 2024. It was noted that most of this study’s patients were private booked patients. Therefore, they wished to have a vaginal delivery with less or no intervention. All subjects had free thyroxine and ionized calcium measured in the first trimester using a Roche 9180 electrolyte analyzer and Cobas Immunoassay. Regardless of the calcium level and preeclampsia risk screening, they all had at least 1500 mg of calcium daily intake during the second and third trimester of pregnancy until labor started. Levothyroxine 100 mg supplemented daily was only given if the pregnant woman had a free thyroxine level of less than 1.1 ng/dL, regardless of the TSH level or sign of subclinical hypothyroidism. Supplementation of levothyroxine 100 mg was stopped when the free thyroxine level was more than 1.4 ng/dL (just below the normal range of our population). We measured potassium levels only at early labor. There was no modification in diet, and the patients continued to take the vitamin and mineral tablets as usual or had previously been prescribed. Patient with a history of previous cesarean section is also included. We measured femur length and head circumference using ultrasound and presented them in the percentile using the Intergrowth chart.
Cervical dilatation found during labor assessments is plotted on the partograph. Labor progressed steadily at varying rates and intensities. A prolonged first stage of labor is defined as the point at which the action line on the partograph is crossed, occurring between the latent phase and full cervical dilatation. The latent phase refers to the period before active labor begins, typically when the cervix dilatation is less than 4 cm. Augmentation in our study is taken only to exclude the diagnosis of CPD when the head station is less than 2/5. The other reason for augmentation is the patient’s request. Five IU of oxytocin and 1 g of calcium gluconate are diluted in 0.9% normal saline, whereby the drop rate can be titrated to achieve regular contractions. Since this study focuses on the prolonged first stage of labor, women with a prolonged second stage were excluded.
In this study, postpartum hemorrhage is defined as total blood loss of 1000 mL or more within 24 hours after the delivery. Meanwhile, puerperal sepsis is defined as a genital tract infection occurring any time between membrane rupture until 42 days postpartum. It is characterized by the presence of at least two of the following signs: pelvic pain, fever, abnormal vaginal discharge, or delayed uterine involution.
13. Results
A total of 2672 of all patients who wished vaginal delivery were included in the study, as shown in Figure 2. Among them, 461 consecutive cases of prolonged labor have been retrospectively reviewed. The incidence of prolonged labor in this study group was 17%. It was noted that 92% of the patients (n = 424) with prolonged labor were private booked patients with consent to refuse augmentation of labor to allow more natural labor progress. This group consisted of patients with allowed slower labor progress, and 28% of them were primipara (n = 129).
Figure 2.
The flow diagram of the study participants.
In this study, 77% of the women had a normal vaginal birth (n = 324) with no augmentation or amniotomy. Augmentation was decided lastly to be given to 93 women to deliver the baby (22%). Most of the labor characteristics in all groups were weak contractions (62%), relative cephalopelvic disproportion (18%) with fetal weight >3400 g, and the occipital posterior position (8%).
The normal prolonged labor group (without augmentation) delivered spontaneously in 39%, using a vacuum in 47%, and forceps in 2%. Regarding the delivery method, there were significant differences in the delivery using a vacuum between the normal prolonged labor group and the prolonged labor with augmentation group (p < 0.011).
This study had no maternal and perinatal mortality (Table 1). Febrile morbidity after parturition was seen in 19 patients, which correlated to the duration of labor. Perinatal morbidity occurred in 19% of the newborns. Maternal morbidities like PPH, UTI, puerperal sepsis, and wound infection were 19%, 7%, 1%, and 1%, respectively, in the normal prolonged labor group. PPH is more frequent in normal prolonged labor without any augmentation. The patients with PPH in all groups had a mean serum ionized calcium level of 2.8 ± 0.35 mg/dL. Although this study did not assess statistical differences in maternal morbidity, patients with the administration of augmentation agents had significantly lower morbidity in percentage terms.
| Normal prolonged labor (n = 324) | Prolonged labor with augmentation (n = 93) | p-value | |
|---|---|---|---|
| Ionized calcium (mg/dL) | 4.6 (+1.6) | 3.9 (+1.9) | 0.03 |
| Free thyroxine (ng/dL) | 0.97 (+0.2) | 0.89 (+0.4) | NS |
| Ultrasonography parameters (in percentile) | |||
| Femur length (FL) | 32% (+9) | 18% (+10) | 0.06 |
| Head circumference (HC) | 56% (+11) | 61% (+8) | NS |
| Method of delivery | |||
| Spontaneous | 126 (35%) | 28 (27%) | NS |
| Vacuum | 152 (42%) | 58 (57%) | 0.009* |
| Forceps | 6 (2%) | 1 (1%) | NS |
| Unknown | 40 (11%) | 6 (6%) | NS |
| Caesarean section | 35 (10%) | 9 (9%) | NS |
| Maternal morbidity | |||
| Postpartum hemorrhage | 62 (19%) | 9 (10%) | NS |
| Urinary tract infection | 23 (7%) | 5 (5%) | NS |
| Puerperal sepsis | 3 (1%) | 1 (1%) | NS |
| Wound infection | 32 (10%) | 0 (0%) | 0.03 |
Table 1.
p-value significant at < 0.05.
No neonatal mortality was found in either group. There was no sufficient neonatal morbidity data collected in both group and normal labor progress group for comparison (our limitation). Femur length in the prolonged labor with augmentation group was shorter than that of the normal prolonged group (percentile 32–18%).
Average calcium and free thyroid levels in the normal prolonged labor group (4.6 mg/dL and 1.01 ng/dL, consecutively) were higher than those of prolonged labor with the augmentation group (3.9 mg/dL and 0.89 ng/dL, consecutively). The prevalence rate of hypocalcemia in this study population was relatively high, at 87%. The mean serum calcium levels were significantly lower in the third trimester than in the second trimester. The limitation of this study is the progress of labor in all the patients taking increased supplementary calcium was not compared with that in control antenatal cases.
14. Discussion
In most cases of regular course of labor, a shorter duration of labor is preferred. There was no possibility of having prolonged labor without an intervention to expedite birth if the partograph table crossed. This study would answer whether pregnant women would have normal prolonged labor if calcium and thyroid factors were well prepared at antenatal care.
In this study, without augmentation, normal prolonged labor is possible. With the incidence of prolonged labor of 17%, measuring and preparing calcium and thyroid at antenatal care is a feasible effort to have an optimal contraction in labor rather than rupturing her membranes or administering oxytocin at labor. One positive side of augmentation in the prolonged labor group is that the vacuum is less applied. The high prevalence of low calcium levels in both groups of this study might cause a shorter femur length than the average growth curve.
This study might embrace diversity in the duration of labor, which might not happen if we applied all laboring women with the same partograph. Moreover, to our knowledge, the present idea in this study is relatively new: allowing some women with slower progress of dilation to have “gentle” birth.
15. Conclusion
Prolonged labor is still challenging for many obstetricians. We believe measuring and supplementing calcium (and thyroid) in everyday labor problems is essential rather than generalizing action to augment contraction when the labor is prolonged. Tapping into a mother’s natural strength and enhancing her labor environment is a gentler and just as effective (if not more so) approach compared to rupturing her membranes or administering oxytocin.
Calcium is a simple, low-cost treatment that could bring more spontaneous vaginal birth by preventing labor dysfunction and its interventions, thereby preventing cesarean section and its morbid complications. Meanwhile, the thyroid hormone influences uterine muscle contraction by acting in smooth muscle cells.
In summary, the roles of calcium and thyroid hormones are critical in shaping the course of labor. A holistic approach to prenatal care that includes calcium and thyroid supplementation can reduce the incidence of prolonged labor or prevent postpartum hemorrhage.
Acknowledgments
Thank you to all colleagues in the Obstetrics Gynecology Department of Cipto Mangunkusumo General Hospital, Faculty of Medicine, Universitas Indonesia.
Conflict of interest
The authors declare no conflict of interest.
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