S. Bhaumik
S. Ghosh
K.K. Haldar*
P.K. Mitra+
B. Manna**

The effects of maternal pre-eclampsia on fetal outcome has been a subject of concern for a long time. Two decades back an association between pre-eclampsia and neonatal neutro-penia (NN) was recognized(1). The low neutrophil count usually resolves before 3 days of age. In the recent past the main focus of workers(2-4) is on the study of the risk of sepsis amongst the infants of pre-eclamptic toxemic mothers (IPETMs) particularly among those with NN. We conducted this prospective study in an inborn population with the objective to find out the risk of early onset septicemia and its relation to neutropenia in the neonates of the pre-eclamptic mothers.

Ninety newborn babies born to mothers with pre-eclampsia in the Department of Gynecology and Obstetrics, R.G. Kar Medical College and Hospital, Calcutta between August, 1996 and July, 1997 were included in the study. Pre-eclamptic mothers were identi-fied by finding hypertension (systolic BP >140 mm of Hg or diastolic BP >90 mm of Hg on two occasions) plus proteinuria and edema(5). Proteinuria was defined as 100 mg/dl or more in atleast two random urine specimens collected 6 or more hours apart.

Babies who met the entry criteria were monitored clinically for 3 days after birth to detect any feature of neonatal septicemia. Early onset sepsis was defined(6) as that which occurred within 3 days (72 hours) of birth. Proven sepsis was identified if a bacterial pathogen was cultured from either blood or CSF. Presumed sepsis was defined as the presence of clinical signs of sepsis in the absence of growth of a micro-organism in culture. To study early onset sepsis for each infant of pre-eclamptic toxemic mother (IPETM) a birth weight and gestational age matched baby (n = 90) was taken from infants born to normal mothes (INMs). The difference in birth weight and gestational age in each pair did not exceed 50 g and 2 weeks, respectively.

The estimations of absolute neutrophil counts (ANC) were done by standard method(7), only for the IPETMs within 12 hours after birth taking capillary blood by warm heel puncture technique. Neonatal neutropenia (NN) was defined as an ANC less than 2.2 ´ 109/L in the first 12 hours of life, the lowest number in the range reported earlier(8).

No case of clinically apparent chorio-amnionitis, genital tract infection and prolonged rupture of membrane were included in any group of study.

Comparison of differences in proportions was made by c2-test and Fisher’s exact test (whenever applicable) while the mean differ-ence in two groups was compared by Student’s t-test. Relative risk and 95% confidence intervals were calculated by using Epi-info 5.0 software package.

The IPETMs and INMs groups were comparable in respect of baby’s gestational age and birth weight (p >0.05). Six neonates of mothers with pre-eclampsia developed early onset sepsis of which 5 had proven and one had presumed sepsis. Two neonates of normal mothers developed sepsis (proven : presumed 1 : 1). There was no significant difference in the incidences of early onset sepsis between the two groups [IPETMs 6.7% (6/90) vs INMs 2.2% (2/90), p >0.10). Early onset septicemia was significantly more frequent amongst neutropenic babies compared to non-neutro-penic ones [17.4% (4/23) vs 3.0% (2/67); p <0.05] (Table I ).

There was a significant trend (p <0.01) of progressive neutropenia with lowering of birth weight. Similarly, with lesser gestational age a trend of lower ANC (p <0.03) was noticed. The birth weight and gestational age along with other clinical parameters in IPETMs in relation with NN are shown in Table II. NN was about three-fold more frequent in IPETMs when maternal hypertension was severe (diastolic ³110 mm of Hg) compared to moderate <110 mm of Hg) [p<0.05].

Table I - Risk of Early Onset Septicemia in IPETMs 

Table II - Various Clinical Parameters in IPETMs in Relation to NN

We found an increased risk, though not statistically significant (p >0.10) of early onset sepsis in babies born to pre-eclamptic mothers (Table I). There are reports of both increased risk(2,4) as well as no risk(3) in these babies. It has been suggested that the increased risk is related to low ANC in the peripheral blood of IPETMs. A significantly increased risk (p <0.05) of septicemia was found in neutropenic IPETMs compared to non-neutropenic ones. The lowering of ANC is due to diminished neutrophil production in the fetus of pre-eclamptic mother(9). The mechanism responsi-ble for diminished neutrophil production is suggested to be due to an inhibitor elaborated by placenta of women with pre-eclampsia(10). However no difference of sepsis between neonates with or without neutropenia has been reported by those workers who found no increased risk of sepsis in IPETMs(3).

In finding out the relationship of NN with early onset sepsis, some recorded clinical characteristics of IPETMs revealed interesting findings (Table II ). NN was more with lower birth weight (p <0.01) and gestational age (p <0.03). It had a direct relationship with severity of hypertension in mothers. These findings are in conformity with earlier reports(3). However, sex of the baby, mode of delivery, duration of rupture of membrane (excluding prolonged rupture) and Apgar score had no significant impact on ANC in IPETMs.

This prospective cohort study started with 90 IPETMs and 90 INMs. But the ultimate sample size of the babies developing early onset septicemia was so small (6 from IPETMs and 2 from INMs) that statistical analysis of sepsis in relation to various clinical parameters was not useful in drawing inferences. A similar study with much larger sample sizes is indicated in this context.

In conclusion, this preliminary study reveals that babies of pre-eclamptic mothers had relatively more risk of developing early onset septicemia than those of normal mothers. This risk was significantly more in neutropenic babies than non-neutropenic ones of pre-eclamptic mothers.

Contributors: SB participated in data collection and drafting of paper; SG co-ordinated the study including design and interpretation and drafted the paper; he will act as guarantor; KKH guided the microbiological aspects; PKM participated in the hematological data quality control; and BM was responsible for statistical analysis.

Funding: None.

Competing interests: None stated.

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