Abstract
70 women who presented with preterm labour were given hydration therapy with 1 litre of Ringer’s lactate solution intravenously over one hour. Those who failed to respond were further treated with intravenous Duvadilan drip. Results were noted as responders and non responders in both the groups in relation to the cervical score at time of presentation. 40 of 54 patients (74.19%) with cervical score of £ 5 responded to hydration therapy. Only 10 of 32 patients (31.25%) with cervical score of > 5 responded to hydration therapy. Hydration therapy seems to be an effective preliminary regime for tocolysis with an efficacy almost equivalent to that of other tocolytic drugs, and no significant adverse effects especially when the patient presents in early preterm labour i.e. cervical score of £ 5.

Introduction
Preterm labour is associated with a high perinatal morbidity and mortality irrespective of the aetiology of preterm onset of labour.

The importance of the day is to find a suitable therapy which will help tackle preterm labour with insignificant side effects.

Maternal hydration therapy seems to be an effective alternate therapeutic option to be practised before embarking on pharmacotherapeutic tocolytic drugs. All available tocolytic drugs have a high percentage of side effects and require intensive maternal haemodynamic monitoring.

This study was undertaken to verify whether hydration therapy is beneficial or not; as previous studies have reported that hydration therapy is not beneficial.^1-3

Material and Methods
70 women who presented with preterm labour were prospectively studied at our tertiary care centre. The women who presented with preterm labour were enquired into and a detailed history especially of symptoms taken, and any high risk factor for preterm labour was studied. Detailed obstetric, menstrual, past significant medical and surgical history was asked for. Patients were then subjected to General and Obstetric examination. Specific note was made of pulse rate, uterine size correlation to menstrual age, uterine activity and Bishop’s cervical score. Clinical correlation to identify Intra uterine growth restriction (IUGR) and oligohydramnios was made. Non stress test was performed to identify the need for immediate delivery; in pregnancy of 32 weeks or more gestational age. Ultrasonography was performed to identify foetal congenital malformations, foetal growth, liquor volume and placental location and maturity. A high vaginal swab was taken for bacterial culture and antibiotic sensitivity test to identify any ascending infection.

The following were the exclusion criteria:

1. Ultrasonography report showing foetal congenital malformations incompatible with life,
2. Established preterm labour (cervix more than 3 cm dilated, cervical effacement of more than 70%).
3. Gestational age more than 37 weeks
4. Rheumatic heart disease or ischaemic heart disease
5. Preterm premature rupture of membranes.

All patients were advised complete bed rest in left lateral position. Injection Betamethasone 12 mg i.m. in two doses 24 hours apart was given to all patients more than 28 weeks and less than 35 weeks gestational age.

All patients were initially given one litre of Ringer lactate intravenously over one hour. At the end of one hour patient was reassessed for amelioration of symptoms and signs. If there was amelioration of symptoms and signs then they were noted as responders. The responders were observed for recurrence of preterm labour and time elapsed for delivery since hydration therapy noted. They were after 24 hours, then started on T. Duvadilan 10 mg four times a day for 7 days. Culture and sensitivity report of high vaginal swab traced and appropriate treatment given as per antibiotic sensitivity report.

If there was no response to hydration therapy, then patient was started immediately on Injection Duvadilan drip i.e. 60 mg of Injection Duvadilan in a pint of 5% Dextrose started at rate of 60 µg/min. Titrated to a maximum of 480 µg/min. Again response to Duvadilan therapy was noted.

Response was assessed in terms of responders and non responders to hydration therapy and Duvadilan drip depending on the Bishop’s cervical score of £ 5 or > 5. Response to both maternal hydration and Duvadilan therapy was assessed in terms of delay in delivery (prolongation of pregnancy); whether delivery occurred within 24 hours, 24-48 hours, after 48 hours but within 7 days, or after 7 days.

Responders were defined as pregnancy prolonged or delivery delayed by 24 hours or more. Those patients who failed to respond or delivered within 24 hours of therapy were defined as non responders.

None of the patients on hydration therapy and Duvadilan drip had any significant side effects related to the therapy.

Results
Preterm birth is the leading cause of neonatal mortality and a substantial portion of all birth related short and long term morbidity. Spontaneous preterm labour is responsible for more than half of preterm births.

In all there were 86 patients included in the study and the characteristics of these patients are enumerated in Table 1.

Of the 86 patients, 50 patients responded to hydration therapy alone, 23 who did not respond to hydration therapy were given Intravenous Duvadilan drip. The remaining 13 patients who had not responded to hydration therapy were in advanced labour and hence could not be given intravenous Duvadilan drip (Table 2).

Of the 86 patients who presented with preterm labour 54 had a Bishop’s cervical score of £ 5, and 32 had a Bishop’s cervical score of > 5. Of the 32 patients with cervical score of > 5, 22 (68.75%) did not respond to hydration therapy. Of the 54 patients with cervical score of £ 5, 40 patients (74%) responded to hydration therapy (Table 3).

These findings suggest that hydration therapy has a favourable outcome in patients presenting early in preterm labour i.e. a cervical score of £ 5.

Hydration has been proposed as a treatment for women with preterm labour. Theoretically, hydration may reduce uterine contractility by increasing uterine blood flow and by decreasing pituitary secretion of anti diuretic hormone and oxytocin.¹

Discussion
Preterm birth is often a preclude to early births and the significant attendant burden of infant morbidity and mortality. Treatment consists of bed rest, hydration, pharmacologic intervention, and combination of these. Early detection and effective management of preterm labour are important strategies for preventing preterm birth, which is the leading cause of infant morbidity and mortality.

The aim of tocolytic therapy is to prolong pregnancy to term or long enough for substantial increases in gestational age and infant birth weight or, at a minimum to prolong gestation while Injection Betamethasone is administered to enhance foetal lung development.

Garite TJ et al presented the novel finding that increasing fluid administration for nulliparous women in labour above rates commonly used (250 ml/hr instead of 125 ml/hr) is associated with a lower frequency of prolonged labour and possibly less need for oxytocin. Thus inadequate hydration in labour may be a factor contributing to dysfunctional labour and possibly caesarean delivery.⁴

Stan C et al reviewed hydration for treatment of preterm labour. Hydration has been proposed as a treatment for women with preterm labour. Theoretically, hydration may reduce uterine contractility by increasing uterine blood flow and by decreasing pituitary secretion of anti diuretic hormone and oxytocin. They concluded that the data are too few to support the use of hydration as a specific treatment for women presenting with preterm labour. The two small studies available do not show any advantage of hydration compared to bed rest alone. Intravenous hydration does not seem to be beneficial, even during the period of evaluation soon after admission, in women with preterm labour. Women with evidence of dehydration may, however, benefit from the intervention.¹

Helfgott et al performed the first randomized trial of hydration and sedation with bed rest alone in the treatment of 119 women in preterm labour. Women randomized to treatment received 500 ml of Ringer solution intravenously over 30 minutes and 8 to 12 mg of intramuscular morphine sulphate. Such therapy was not found to be more beneficial than bed rest.²

Huddleston JF et al states that a rapid expansion of the maternal vascular volume by 500 to 1000 ml probably augments cardiac output and uterine blood flow; a fluid load thus presumably helps stabilize decidual lysosomes. Alternatively, volume expansion might depress the release of oxytocin from the posterior pituitary. The potentially adverse effects of rapid intravascular volume expansion are mainly restricted to women with abnormalities in the cardiopulmonary or renal systems. Clearly, a woman labouring with severe mitral stenosis could develop pulmonary oedema with such therapy, as could certain patients with severe hypertension diseases or with limitations of renal function. Generally, a gravida who is being evaluated for possible preterm labour, in addition to being placed in a lateral recumbent position with an electronic (external) contraction monitor in place, is administered a fluid load before being given any other therapy. Frequently, and particularly in the case of a gravida for whom the diagnosis of labour is doubtful or uncertain, the contractions effectively cease. A Cause-and-effect relationship between a fluid load and cessation of contractions is difficult to establish, but administration of some of the more potent therapies, with their potential far more serious side effects, can often be obviated.³

In our study, hydration therapy had an overall success rate of 58.6% (remained undelivered) after 7 days.

Tocolysis achieved after 7 days was in 74.19% when cervical score was £ 5 whereas only 31.25% when cervical score was > 5. Therefore patients with preterm labour who have a cervical score of £ 5 on presentation respond favourably to hydration therapy.

In comparison as can be observed from Table 4, Ritodrine had prolonged pregnancy in 72%⁵ and 42.30%⁶ at 7 days in two different studies. In another study by Garcia-Velasco et al 92.31% remained undelivered after 48 hours with Ritodrine therapy.⁷

One of the most serious complications of beta agonist therapy is pulmonary oedema. Multiple gestations, polyhydramnios, excessive fluid administration (especially with physiologic solutions), anaemia, and hypertension are associated with increased risk for development of pulmonary oedema during therapy. It is uncommon for pulmonary oedema to occur in the first 24 hours of therapy, with more than 90% of reported cases occurring after 24 hours of treatment.⁸ In our study there were no significant complications reported.

We can conclude that the benefits of hydration therapy are:

1. No cost of drugs, as no drugs are required.
2. Drugs have to be administered over prolonged period whereas hydration therapy is completed in an hour’s time.
3. When patient is to be transferred from a peripheral hospital to a central institution then hydration therapy can easily be given in transit without risk of drug related side effects and no intensive monitoring required.
4. Simultaneous administration of Injection Betamethasone and tocolytic drugs run risk of pulmonary oedema. The risk of pulmonary oedema is less in patients with hydration therapy by the time Injection Betamethasone action begins to start, the hydration therapy is over.

Conclusions
Management of women with preterm labour poses challenge to the Obstetrician. Hydration therapy seems to be an effective preliminary regime for tocolysis with an efficacy almost equal to that of other tocolytic drugs, and no significant adverse effects especially when the patient presents in early preterm labour i.e. cervical score of less than or equal to 5.

References

1. Stan C, Boulvain M, Hirsbrunner-Amagbaly PJ, Pfister R. Hydration for treatment of preterm labor. Cochrane Database Syst Rev 2002; 2 : CD003096.
2. Helfgott AW, Willis DC, Blanco JD. Is hydration and sedation beneficial in the treatment of threatened preterm labor? A preliminary report. J Mayern Fetal Med 1994; 3 : 37-42.
3. Huddleston JF, Luis Sanchez-Ramos, Huddleston KW. Acute management of preterm labor. In : Clinics in Perinatology. Copyright WB Saunders Company. 2003; 30 : 4.
4. Garite TJ, Weeks J, Peters-Phain K, Pattillo C, Brentos WR. A randomized controlled trial of the effect of increased intravenous hydration on the course of labor in nulliparous women. Am J Obstet Gynecol 2000; 183 (6) : 1544-48.
5. Hollander DI, Nagey DA, Pupkin MJ. Magnesium sulfate and ritodrine hydrochloride : A randomized comparison. Am J Obstet Gynecol 1987; 156 (3) : 631-37.
6. Papatsonis DN, Van Geijn HP, Ader HK, et al. Nifedipine and ritodrine in the management of preterm labor : A randomized Multi center trial. Obstet Gynecol 1997; 90 (2) : 230-34.
7. Garcia-Velasco JA, Gonzalez GA. A prospective randomized trial of nifedipine vs. ritodrine in threatened preterm labor. Int J Gynecol Obstet 1998; 6 : 239-44.
8. Lam F, Elliot J, Jones JS, et al. Clinical issues surrounding the use of terbutaline sulfate for preterm labor. Obstet Gynecol Surv 1998; 53 (1) : 585-95.

*Lecturer; **Chief Resident; ***Professor and Head of Department of Obstetrics and Gynaecology, Seth GS Medical College, KEM Hospital, Parel, Mumbai.